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1.
Acta Vet Hung ; 72(1): 24-32, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38578702

RESUMEN

Feeding costs of farmed insects may be reduced by applying alternative nitrogen sources such as urea that can partly substitute true proteins. The aim of this study was to examine the effects of different nitrogen sources on body weight (BW) and survival rate (SR) of the Jamaican field cricket (JFC, Gryllus assimilis), the house cricket (HC, Acheta domesticus), yellow mealworm larvae (YM, Tenebrio molitor) and superworm larvae (SW, Zophobas morio). Crickets were either housed individually or in groups, and larvae were group-housed. Six isonitrogenous feeds composed of 3.52% nitrogen were designed for all four insect species using four independent replicates with micellar casein: urea proportions of 100-0%, 75-25%, 50-50%, 25-75%, 0-100% and 100% extracted soybean meal. All selected insect species were able to utilise urea. However, urea as the only nitrogen source resulted in low final BW. In the HC, the JFC, and the YM on nitrogen basis urea can replace 25% of micellar casein without having any negative effects on BW and SR in comparison to the 100% micellar casein group. In the SW, a 25% urea level did not have a significant effect on final BW, but SR decreased significantly.


Asunto(s)
Escarabajos , Gryllidae , Tenebrio , Animales , Caseínas/metabolismo , Insectos , Larva/metabolismo , Tenebrio/metabolismo , Peso Corporal , Nitrógeno , Suplementos Dietéticos
2.
Sci Rep ; 14(1): 8043, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580733

RESUMEN

Bisphenol-A (BPA) is widely used in food packaging and household products, leading to daily human exposure and potential health risks including metabolic diseases like type 2 diabetes mellitus (T2DM). Understanding BPA's mechanisms and developing intervention strategies is urgent. Centella asiatica, a traditional herbal medicine containing pentacyclic triterpenoids, shows promise due to its antioxidant and anti-inflammatory properties, utilized for centuries in Ayurvedic therapy. We investigated the effect of Centella asiatica (CA) ethanol extract on BPA-induced pancreatic islet toxicity in male Swiss albino mice. BPA administration (10 and 100 µg/kg body weight, twice daily) for 21 days caused glucose homeostasis disturbances, insulin resistance, and islet dysfunction, which were partially mitigated by CA supplementation (200 and 400 mg/kg body weight). Additionally, heightened oxidative stress, elevated levels of proinflammatory cytokines, loss of mitochondrial membrane potential (MMP), abnormal cell cycle, and increased apoptosis were implicated in the detrimental impact of BPA on the endocrine pancreas which were effectively counteracted by CA supplementation. In summary, CA demonstrated a significant ability to mitigate BPA-induced apoptosis, modulate redox homeostasis, alleviate inflammation, preserve MMP, and regulate the cell cycle. As a result, CA emerged as a potent agent in neutralizing the diabetogenic effects of BPA to a considerable extent.


Asunto(s)
Centella , Diabetes Mellitus Tipo 2 , Islotes Pancreáticos , Fenoles , Ratones , Animales , Masculino , Humanos , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Islotes Pancreáticos/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Compuestos de Bencidrilo/farmacología , Peso Corporal
3.
J Anim Sci ; 1022024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38571338

RESUMEN

A total of 720 barrows (line 200 × 400, DNA genetics) were used in two 42-d nursery trials (initially 6.20 ±â€…0.12 kg and 5.63 ±â€…0.16 kg, respectively) to evaluate strategies for allotting pigs to pens in randomized controlled trials. At placement, the population was split into three cohorts with similar average weight and standard deviation and randomly assigned to one of the three allotment strategies. Strategy 1 (random) utilized a simple randomization strategy with each pig randomized to pens independent of all other pigs. Strategy 2 (body weight [BW] distribution) sorted each pig within the cohort into one of the five BW groups. One pig from each weight group was then randomly assigned to a pen such that distribution of BW within pen was uniform across pens. Strategy 3 (BW grouping) sorted pigs within the cohort into 3 BW categories: light, medium, and heavy. Within each BW category, pigs were randomized to pen to create pens of pigs from each BW category. Within each experiment, there were 72 pens with five pigs per pen and 24 pens per allotment strategy. For all strategies, once pigs were allotted to pens, pens were allotted to one of the two treatments for a concurrent trial. In experiment 1, environmental enrichment using ropes tied near the pan of the feeder was compared to a control with no enrichment. In experiment 2, treatment diets consisted of basal levels of Zn and Cu from the trace mineral premix for the duration of the study (110 and 17 mg/kg, respectively; control), or diets (supplemented control) with carbadox (50 g/ton; Mecadox, Phibro Animal Health, Teaneck, NJ) fed in phase 1 (days 0 to 22) and 2 (days 22 to 43), pharmacological levels of Zn and Cu (2,414 mg/kg Zn from ZnO; 168 mg/kg Cu from CuSO4) fed in phase 1, and only pharmacological levels of Cu (168 mg/kg Cu from CuSO4) fed in phase 2. These treatment designs were used to determine the impact on coefficient of variation (CV) and to estimate the number of replications required to find significant treatment differences based on allotment strategy. There were no meaningful allotment strategy × treatment interactions for either study. For between-pen CV, pigs allotted using BW distribution and BW grouping strategies had the lowest CV at allotment and final weight in both trials. For overall average daily gain in experiments 1 and 2 in experiment 2, the BW distribution strategy required the fewest replications to detect differences in performance. However, there is no meaningful difference between allotment strategies in replications required to detect significant differences for gain:feed ratio.


Decreasing variation between experimental units increases the likelihood of finding a statistically significant difference if one exists. Assignment of animals to experimental units (pens) may contribute to that variation. Therefore, the purpose of this trial was to investigate the effect that different methods of allotting pigs to pens (experimental unit) have on variation and in turn, the number of replications required to detect a significant difference of a given amount between treatments. The random strategy assigned pigs to pens in a completely random fashion. The body weight (BW) distribution strategy ordered pigs from lightest to heaviest and created five groups based on BW. Each pen was randomly assigned one pig from each of the five groups. The BW grouping strategy again ordered pigs from lightest to heaviest but split pigs into three groups based on BW and each pen was randomly assigned pigs from only one BW group such that there were pens of light pigs, pens of medium pigs, and pens of heavy pigs. Ultimately, the best allotment strategy depends on the parameter of interest. For final BW and overall ADG, the BW grouping method required the fewest pens to detect statistically significant differences.


Asunto(s)
Crianza de Animales Domésticos , Animales , Masculino , Porcinos , Crianza de Animales Domésticos/métodos , Distribución Aleatoria , Peso Corporal , Alimentación Animal/análisis , Dieta/veterinaria
4.
PLoS One ; 19(4): e0301012, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38573884

RESUMEN

Different functional foods with bioactive nutrients are being explored for the management of NAFLD. Whey proteins are rich in bioactive peptides and are suggested to show antioxidant and anti-inflammatory effects. We aim to test the hypothesis that the whey protein supplementation following a high fat-high fructose (HFHF) diet would protect against liver damage, inflammation, endotoxemia and steatosis in male Wistar rats. 36 rats were randomized into four groups for 8 weeks as the HFHF diet group, HFHF diet and whey protein isolate (WPI-200mg/kg/day) group (HFHF+WPI), control (C) group, and C+WPI (200mg/kg/day) group. Rats fed with a HFHF diet had higher final body weight compared to C and C+WPI groups (p = 0.002). Thus, WPI showed no significant effects for the body weight of rats with a HFHF diet. On the other hand, the HFHF+WPI group had significantly lower abdominal circumference when compared with the HFHF group (p<0,001). Higher serum CRP levels were observed in the groups with a HFHF diet (p<0,001) and WPI supplementation showed no effects on CRP levels. Whey protein supplementation resulted with lower total liver damage score in HFHF+WPI group compared with the HFHF diet group (p<0,001). Conversely, higher liver damage scores were observed with the C+WPI group compared to C group (p<0,001). HFHF diet resulted with higher expression of TLR-4 in the liver meanwhile WPI supplementation showed no effects on liver TLR-4 expression. We observed higher colon Occludin expression in HFHF+WPI and C+WPI groups compared with HFHF and C groups (p<0,001). Our results showed that, whey protein supplementation might help improve liver damage associated with a high fat-high fructose diet and increase the expression of Occludin in the small intestine and colon.


Asunto(s)
Fructosa , Receptor Toll-Like 4 , Ratas , Masculino , Animales , Proteína de Suero de Leche/farmacología , Ratas Wistar , Fructosa/efectos adversos , Ocludina , Dieta Alta en Grasa/efectos adversos , Hígado , Peso Corporal , Suplementos Dietéticos
5.
Zhongguo Zhen Jiu ; 44(4): 441-448, 2024 Apr 12.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38621732

RESUMEN

OBJECTIVES: To observe the effects of electroacupuncture (EA) with "intestinal disease prescription" on the intestinal mucosal barrier and NLRP3 inflammasome in rats with dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC), and explore the underlying mechanism of EA with "intestinal disease prescription" for the treatment of UC. METHODS: Thirty-two healthy male SPF-grade SD rats were randomly divided into a blank group, a model group, a medication group, and an EA group, with 8 rats in each group. Except for the blank group, the UC model was established by administering 5% DSS solution for 7 days. After modeling, the rats in the medication group were treated with mesalazine suspension (200 mg/kg) by gavage, while the rats in the EA group were treated with acupuncture at bilateral "Tianshu" (ST 25), "Shangjuxu" (ST 37) and "Zhongwan" (CV 12), with the ipsilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37) connected to the electrodes of the EA instrument, using disperse-dense wave, with a frequency of 10 Hz/50 Hz, and each intervention lasted for 20 minutes. Both interventions were performed once daily for 3 days. The general conditions of rats were observed daily. After intervention, the disease activity index (DAI) score was calculated; colon tissue morphology was observed using HE staining; serum levels of pro-inflammatory cytokines (interleukin [IL]-18, IL-1ß) were measured by ELISA; protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in colon tissues was detected by Western blot; positive expression of zonula occludens-1 (ZO-1) and Occludin in colon tissues was examined by immunofluorescence. RESULTS: Compared with the blank group, the rats in the model group exhibited poor general conditions, slow body weight gain, shortened colon length (P<0.01), increased DAI score and spleen index (P<0.01), elevated serum IL-18 and IL-1ß levels, and increased protein expression of NLRP3, ASC, and Caspase-1 in colon tissues (P<0.01), along with decreased positive expression of ZO-1 and Occludin in colon tissues (P<0.01). Compared with the model group, the rats in the medication group and the EA group exhibited improved general conditions, accelerated body weight gain, increased colon length (P<0.05), reduced DAI scores and spleen indexes (P<0.05), decreased serum IL-18 and IL-1ß levels, and lower protein expression of NLRP3, ASC and Caspase-1 in colon tissues (P<0.05), as well as increased positive expression of ZO-1 and Occludin in colon tissues (P<0.05). There were no significant differences in the above indexes between the medication group and the EA group (P>0.05). Compared with the blank group, the rats in the model group exhibited disrupted colon mucosal morphology, disordered gland arrangement, and atrophy of crypts, along with significant inflammatory cell infiltration. Compared with the model group, the rats in both the medication group and the EA group showed relatively intact colon mucosal morphology, with restored and improved gland and crypt structures, and reduced inflammatory cell infiltration. CONCLUSIONS: EA with "intestinal disease prescription" has a significant therapeutic effect on DSS-induced UC, possibly by regulating the expression of NLRP3 inflammasome and proteins related to the intestinal mucosal barrier, thereby alleviating symptoms of ulcerative colitis.


Asunto(s)
Colitis Ulcerosa , Electroacupuntura , Ratas , Masculino , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/terapia , Inflamasomas/efectos adversos , Interleucina-18 , Ratas Sprague-Dawley , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ocludina , Peso Corporal , Caspasas/efectos adversos
6.
Zhongguo Zhong Yao Za Zhi ; 49(3): 763-769, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621880

RESUMEN

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.


Asunto(s)
Compuestos Azo , Dieta Alta en Grasa , Enfermedad del Hígado Graso no Alcohólico , Ratones , Ratas , Animales , Dieta Alta en Grasa/efectos adversos , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/farmacología , Caveolina 1/metabolismo , Caveolina 1/farmacología , Ratones Endogámicos C57BL , Hígado , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Triglicéridos/metabolismo , Peso Corporal , Adenosina Trifosfato/farmacología
7.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1082-1090, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621915

RESUMEN

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.


Asunto(s)
Síndrome del Ovario Poliquístico , Humanos , Ratas , Femenino , Animales , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Proteína X Asociada a bcl-2 , Solución Salina , Ratas Sprague-Dawley , Atresia Folicular , Transducción de Señal , Peso Corporal , Hormona Folículo Estimulante , ARN Mensajero
8.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1266-1274, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621974

RESUMEN

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.


Asunto(s)
Anexina A1 , Neoplasias Asociadas a Colitis , Colitis , Medicamentos Herbarios Chinos , Ratones , Animales , Colitis/complicaciones , Colitis/tratamiento farmacológico , Colitis/genética , beta Catenina/genética , beta Catenina/metabolismo , Ciclina D1/metabolismo , Fusobacterium nucleatum/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Antígeno Ki-67/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Ratones Endogámicos C57BL , Cadherinas/metabolismo , Peso Corporal , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Azoximetano
9.
Proc Natl Acad Sci U S A ; 121(18): e2322692121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38652744

RESUMEN

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin (POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis-acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2.1, and ERα. We found that nPE3 originated in the lineage leading to placental mammals and remained under purifying selection in all mammalian orders, although it was lost in Simiiformes (monkeys, apes, and humans) following a unique segmental deletion event. Interestingly, ablation of nPE3 from the mouse genome led to a drastic reduction (>70%) in hypothalamic Pomc mRNA during development and only moderate (<33%) in adult mice. Comparison between double (nPE1 and nPE2) and triple (nPE1, nPE2, and nPE3) enhancer mutants revealed the relative contribution of nPE3 to hypothalamic Pomc expression and its importance in the control of food intake and adiposity in male and female mice. Altogether, these results demonstrate that nPE3 integrates a tripartite cluster of partially redundant enhancers that originated upon a triple convergent evolutionary process in mammals and that is critical for hypothalamic Pomc expression and body weight homeostasis.


Asunto(s)
Peso Corporal , Ingestión de Alimentos , Elementos de Facilitación Genéticos , Hipotálamo , Proopiomelanocortina , Pez Cebra , Animales , Proopiomelanocortina/metabolismo , Proopiomelanocortina/genética , Ratones , Hipotálamo/metabolismo , Ingestión de Alimentos/genética , Ingestión de Alimentos/fisiología , Pez Cebra/genética , Pez Cebra/metabolismo , Femenino , Masculino , Ratones Transgénicos , Humanos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Mamíferos/metabolismo , Mamíferos/genética
10.
Trop Anim Health Prod ; 56(4): 131, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38637421

RESUMEN

Forty-eight weaned male New Zealand White rabbits aged 6 weeks with an initial body weight of (709.67 ± 13 g) were randomly divided into six experimental groups (8 rabbits each) for 6-14 weeks of age experimental periods. The present study was planned to evaluate the effect of using different forms of Selenium element (inorganic, nanoparticles and organic) as dietary supplementation on productive performance of rabbits. Six experimental groups in completely randomized design were used. The first group (G1, control) was fed the basal diet to cover maintenance and production allowances. Rabbits in the other groups G2, G3, G4 and G5 were fed the basal diet supplemented with Nano- Se at 0.02, 0.03, 0.04 and 0.05 mg/kg diet, respectively. The 6th group (G6) was fed the basal diet supplemented with 0.1 mg/kg diet of salinized yeast (Se-yeast) as organic form. The results indicated that the highest values of nitrogen free extract (NFE) and crude fiber (CF) digestibility, live body weight, daily weight gain, hot carcass weight and dressing percentage were observed with those supplemented with Nano-Se at all levels compared with other treatments. However, feed conversion, net revenue and economic efficiency values were improved with Nano-Se groups followed by organic Se group in comparisons with the control group. Conclusively, the Nano-Se in rabbit's diet has a positive effect in improving rabbit's performance and economic efficiency compared to the inorganic Selenium.


Asunto(s)
Selenio , Animales , Masculino , Conejos , Alimentación Animal/análisis , Peso Corporal , Dieta/veterinaria , Suplementos Dietéticos , Saccharomyces cerevisiae , Selenio/farmacología
11.
Int J Toxicol ; 43(4): 407-420, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38647416

RESUMEN

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.


Asunto(s)
Relación Dosis-Respuesta a Droga , Lactoferrina , Ratas Sprague-Dawley , Proteínas Recombinantes , Animales , Lactoferrina/toxicidad , Proteínas Recombinantes/toxicidad , Masculino , Femenino , Humanos , Ratas , Nivel sin Efectos Adversos Observados , Administración Oral , Peso Corporal/efectos de los fármacos , Saccharomycetales
12.
J Trace Elem Med Biol ; 84: 127450, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38643593

RESUMEN

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s-1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health.


Asunto(s)
Diabetes Mellitus Experimental , Hemorreología , Ratas Wistar , Zinc , Animales , Zinc/sangre , Zinc/farmacología , Masculino , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas , Hemorreología/efectos de los fármacos , Glucemia/metabolismo , Viscosidad Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Peso Corporal/efectos de los fármacos , Suplementos Dietéticos
13.
Sci Rep ; 14(1): 7657, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561353

RESUMEN

The present study was conducted to assess the impact of non-encapsulated, air-dried microencapsulated, and lyophilized microencapsulated probiotics in indigenous cattle calves (Bos indicus). Twenty-four (5-7 days old) indigenous cattle calves were selected and assigned into four groups, with six calves in each as follows: control (CON), fed milk and basal diet alone, and treatment groups supplemented with non-encapsulated (NEC), air-dried microencapsulated (AEC) and lyophilized microencapsulated (LEC) probiotic L. reuteri SW23 at 108 CFU/head/day in skim milk as a carrier provided for 60 days. The animals were divided into four groups, adopting a complete randomized design, and the effects were considered significant at p ≤ 0.05. Probiotics supplementation increased (p < 0.05) body weight gain (kg), average daily gain, and structural growth measurements in calves of all treatment groups. Dry matter intake (g/d), feed conversion efficiency, and fecal counts of Lactobacilli and Bifidobacteria were also increased in the treatment groups compared to CON. The fecal consistency index was highest in CON (0.70 ± 0.03), followed by NEC (0.68 ± 0.01), AEC (0.66 ± 0.02), and LEC (0.65 ± 0.02). Fecal pH and ammonia levels were reduced (p < 0.05) in the probiotic-fed groups compared to CON, with a concomitant increase in fecal lactate, acetate, and propionate levels. In addition, cell-mediated and humoral immunity were significantly increased in supplemented groups as compared to CON. Thus, it can be concluded that supplementation of the probiotics in microencapsulated/non-encapsulated forms to neonatal calves had a variety of positive effects on their health, including better performance, improved gut health, and a lower fecal consistency index. Moreover, among all supplemented groups, the lyophilized microencapsulated group outperformed air-dried microencapsulated and non-microencapsulated groups in terms of ADG, DMI, and gut health.


Asunto(s)
Limosilactobacillus reuteri , Probióticos , Animales , Bovinos , Alimentación Animal/análisis , Peso Corporal , Dieta/veterinaria , Suplementos Dietéticos , Ácido Láctico , Probióticos/farmacología , Destete
14.
J Dev Orig Health Dis ; 15: e5, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563206

RESUMEN

Early supplementation with oregano essential oil (EO) in milk replacer (MR) may improve growth, immune responses, the microbiota and the metabolome in dairy calves during pre-weaning and in adulthood. Sixteen female dairy calves (3 days of age) were divided in two groups (n = 8/group): the control group (no EO) and the EO group (0.23 ml of EO in MR during 45 days). After weaning, calves were kept in a feedlot and fed ad libitum. The animals were weighed, and blood and faecal samples were collected on days 3 (T0), 45 (T1) and 370 (T2) to measure the biochemical profile and characterise peripheral blood mononuclear cells (PBMCs; CD4+, CD8+, CD14+, CD21+ and WC1+), the metabolome and microbiota composition. The EO group only had greater average daily weight gain during the suckling (EO supplementation) period (P = 0.030). The EO group showed higher average CD14+ population (monocytes) values, a lower abundance of Ruminococcaceae UCG-014, Faecalibacterium, Blautia and Alloprevotella and increased abundances of Allistipes and Akkermansia. The modification of some metabolites in plasma, such as butyric acid, 3-indole-propionic acid and succinic acid, particularly at T1, are consistent with intestinal microbiota changes. The data suggest that early EO supplementation increases feed efficiency only during the suckling period with notable changes in the microbiota and plasma metabolome; however, not all of these changes can be considered desirable from a gut health point of view. Additional research studies is required to demonstrate that EOs are a viable natural alternative to antibiotics for improving calf growth performance and health.


Asunto(s)
Dieta , Aceites Volátiles , Animales , Bovinos , Femenino , Leche , Leucocitos Mononucleares , Alimentación Animal/análisis , Destete , Aumento de Peso , Metaboloma , Suplementos Dietéticos , Peso Corporal
15.
Nutrients ; 16(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38612951

RESUMEN

BACKGROUND: The study investigated the impact of starch degradation products (SDexF) as prebiotics on obesity management in mice and overweight/obese children. METHODS: A total of 48 mice on a normal diet (ND) and 48 on a Western diet (WD) were divided into subgroups with or without 5% SDexF supplementation for 28 weeks. In a human study, 100 overweight/obese children were randomly assigned to prebiotic and control groups, consuming fruit and vegetable mousse with or without 10 g of SDexF for 24 weeks. Stool samples were analyzed for microbiota using 16S rRNA gene sequencing, and short-chain fatty acids (SCFA) and amino acids (AA) were assessed. RESULTS: Results showed SDexF slowed weight gain in female mice on both diets but only temporarily in males. It altered bacterial diversity and specific taxa abundances in mouse feces. In humans, SDexF did not influence weight loss or gut microbiota composition, showing minimal changes in individual taxa. The anti-obesity effect observed in mice with WD-induced obesity was not replicated in children undergoing a weight-loss program. CONCLUSIONS: SDexF exhibited sex-specific effects in mice but did not impact weight loss or microbiota composition in overweight/obese children.


Asunto(s)
Obesidad Infantil , Solanum tuberosum , Niño , Humanos , Masculino , Femenino , Animales , Ratones , Dextrinas , Dieta Occidental , Disbiosis , Sobrepeso , ARN Ribosómico 16S/genética , Peso Corporal , Almidón/farmacología , Frutas
16.
J Agric Food Chem ; 72(11): 5734-5745, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38453725

RESUMEN

Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons of the substantia nigra (SN), with neuroinflammation and mitochondrial dysfunction being key contributors. The neuroprotective potential of folic acid (FA) in the dopaminergic system of PD was assessed in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. MPTP (20 mg/kg of body weight) was administered to C57BL/6J mice to simulate PD symptoms followed by FA treatment (5 mg/kg of body weight). Behavioral tests, pole, rotarod, and open-field tests, evaluated motor function, while immunohistochemistry, ELISA, RT-qPCR, and Western blotting quantified neuroinflammation, oxidative stress markers, and mitochondrial function. FA supplementation considerably improved motor performance, reduced homocysteine levels and mitigated oxidative damage in the SN. The FA-attenuated activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome lessened glial cell activity and reduced neuroinflammation. At the molecular level, FA reduced DNA damage, downregulated phosphorylated p53, and induced the expression of peroxisome proliferator-activated receptor α coactivator 1α (PGC-1α), enhancing mitochondrial function. Therefore, FA exerts neuroprotection in MPTP-induced PD by inhibiting neuroinflammation via NLRP3 inflammasome suppression and promoting mitochondrial integrity through the p53-PGC-1α pathway. Notable limitations of our study include its reliance on a single animal model and the incompletely elucidated mechanisms underlying the impact of FA on mitochondrial dynamics. Future investigations will explore the clinical utility of FA and its molecular mechanisms, further advancing it as a potential therapeutic for managing and delaying the progression of PD.


Asunto(s)
Intoxicación por MPTP , Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratones , Animales , Inflamasomas/genética , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos , Neuronas Dopaminérgicas , Intoxicación por MPTP/tratamiento farmacológico , Intoxicación por MPTP/metabolismo , Enfermedades Neuroinflamatorias , Proteína p53 Supresora de Tumor/metabolismo , Ratones Endogámicos C57BL , Enfermedad de Parkinson/genética , Mitocondrias/metabolismo , Peso Corporal , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología
17.
Sci Rep ; 14(1): 6409, 2024 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-38494538

RESUMEN

Dysregulation of key transcription factors involved in hepatic energy metabolism, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and liver X receptor alpha (LXRα), has been observed in T2DM. The present study aims to investigate the effects of aerobic training and vitamin D supplementation on liver enzyme levels and the levels of PGC-1α and LXRα proteins in hepatocytes, in a rat model of T2DM. The study involved 56 male Wistar rats, divided into two groups: one was non-diabetic and acted as a control group (n = 8), and the other had induced diabetes (n = 48). The diabetic rats were then split into six subgroups: two groups received high or moderate doses of vitamin D and aerobic training (D + AT + HD and D + AT + MD); two groups received high or moderate doses of vitamin D alone (D + HD and D + MD); one group underwent aerobic training with vehicle (sesame oil; D + AT + oil), and one group was a diabetic control receiving only sesame oil (oil-receiving). The D + AT + HD and D + HD groups received 10,000 IU of vitamin D, while the D + AT + MD and D + MD groups received 5000 IU of vitamin D once a week by injection. The D + AT + oil group and the sham group received sesame oil. After eight weeks of treatment, body weight, BMI, food intake, serum insulin, glucose, 25-hydroxyvitamin D, ALT, AST, and visceral fat were measured. The levels of PGC-1α and LXRα proteins in the liver was assessed by western blotting. Statistical analysis was performed using the paired t-test, one-way analysis of variance (ANOVA), and the Tukey post hoc test at a significance level of P < 0.05. Body weight, food intake, and BMI decreased significantly in the D + AT + HD, D + AT + MD, D + AT + oil, D + HD, and D + MD groups with the highest reduction being observed in body weight and BMI in the D + AT + HD group. The D + AT + HD group exhibited the lowest levels of insulin, glucose, and HOMA-IR while the D + C group exhibited the highest levels among the diabetic groups. The D + AT + HD and D + AT + MD groups had lower levels of ALT and AST enzymes compared to the other groups with no significant difference between D + AT + HD and D + AT + MD. D + AT + HD (p = 0.001), D + AT + MD (p = 0.001), D + HD (p = 0.023), D + MD (p = 0.029), and D + AT + oil (p = 0.011) upregulated LXRα compared to D + C. Among these groups, D + AT + HD exhibited a more profound upregulation of LXRα than D + AT + MD, D + AT + oil, D + HD, and D + MD (p = 0.005; p = 0.002, p = 0.001, and p = 0.001, respectively). Similarly, D + AT + HD showed a more notable upregulation of PGC-1α compared to D + AT + oil, D + HD, and D + MD (p = 0.002; p = 0.001, and p = 0.001, respectively). Pearson correlation tests showed significant and negative correlations between serum 25-hydroxyvitamin levels and both visceral fat (r = - 0.365; p = 0.005) and HOMA-IR (r = - 0.118; p = 0.009); while positive and significant correlations between the liver-to-bodyweight ratio with both ALT and AST enzymes and also between QUICKI levels with LXRα (r = 0.578; p = 0.001) and PGC-1α (r = 0.628; p = 0.001). Combined administration of aerobic training and vitamin D supplementation potentially improves liver enzymes in type-2 diabetic rats that were simultaneous with upregulating the levels of PGC-1α and LXRα proteins in hepatocytes. These improvements were more significant when combining exercise with high-dose vitamin D supplementation. This study highlights the potential of this combination therapy as a new diabetes treatment strategy.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Masculino , Ratas , Animales , Receptores X del Hígado/genética , Diabetes Mellitus Experimental/terapia , Aceite de Sésamo , Ratas Wistar , Vitamina D/farmacología , Vitaminas , Insulina , Hígado , Peso Corporal , Glucosa , Diabetes Mellitus Tipo 2/tratamiento farmacológico
18.
PLoS One ; 19(3): e0294999, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38483938

RESUMEN

Allium Cepa Linn. (Onions) has extensively been used in traditional medicine, is one of the important Allium species regularly used in our daily diet, and has been the source of robust phenolic compounds. The current study is intended to evaluate the fecundity-enhancing effect of A. Cepa on the reproductive performance of two successive generations of rats; F0 and F1. A. Cepa extract was initially tested for in vitro antioxidant assay via DPPH and ROS, followed by in vivo toxicity testing. In the fecundity assessment, eighteen pairs of male and female rats (n = 36, 1:1, F0 generation) were divided into three groups and dosed with 75mg/kg and 150 mg/kg daily of A. Cepa extract and saline respectively, up to pre-cohabitation, cohabitation, gestation and lactation period. The reproductive performance, including body weight, live birth index, fertility index, and litter size, was assessed. Various parameters like Hematological, Hormonal (FSH, LH, Testosterone, estradiol), antioxidant markers (SOD, Glutathione peroxidase) and lipid profile of F0 and F1 generations were assessed with evaluation of histopathology of male and female organs. Ethanolic extract of A. Cepa showed the greatest antioxidant potential in DPPH and ROS methods. The continued exposure of the F0 and F1 generations to A. Cepa extract did not affect body weight, fertility index, litter size, and survival index. However, semen pH, sperm motility, sperm count, sperm viability, and semen volume were significantly improved in both generations. We have found pronounced fecundity outcomes in both genders of F0 and F1 generations with A. Cepa 150mg/kg/day extract as compared to control. Results showed that A. Cepa significantly increased (P < 0.05) hemoglobin, follicular stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone and glutathione peroxidase activities, while total lipid, LDL, and cholesterol were significantly decreased (P < 0.05) in both generations. Histology of both generations of animals reveals enhanced spermatogenesis and enhanced folliculogenesis with improved architecture. Altogether, the present results suggest that A. Cepa extract improved fecundity in both male and female rats by improving hormonal activities and oxidative stress.


Asunto(s)
Antioxidantes , Cebollas , Ratas , Masculino , Femenino , Animales , Especies Reactivas de Oxígeno/farmacología , Antioxidantes/farmacología , Motilidad Espermática , Semillas , Reproducción , Fertilidad , Peso Corporal , Testosterona , Hormona Luteinizante/farmacología , Hormona Folículo Estimulante/farmacología , Glutatión Peroxidasa , Lípidos/farmacología
19.
Eur Rev Med Pharmacol Sci ; 28(5): 1680-1694, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38497852

RESUMEN

OBJECTIVE: The goal of this study was to investigate the potential protective effect of L-carnitine (20 mg/kg bw, 1/20 LD 50) against aluminum chloride (AlCl3) on the quality of the male rats' testicles and sperm, as well as to determine whether or not the effects of AlCl3 could be counteracted by using L-carnitine as an antioxidant. MATERIALS AND METHODS: Six groups of 36 adult male albino rats (n=6) were randomly formed. In Group I (Gp I), saline injection was given orally as a control. Group II (Gp II) was injected orally with 75 mg/kg body weight of L-carnitine. Group III (Gp III) was given a high dose of L-carnitine (150 mg/kg body weight) orally, while Group IV (G IV) was given a low dose of AlCl3 (20 mg/kg body weight). Group V (Gp V) was given an oral injection of AlCl3 (20 mg/kg) and L-carnitine (75 mg/kg body weight). Group VI (Gp VI) was given AlCl3 at a dose of 20 mg/kg and L-carnitine at a dose of 150 mg/kg body weight for 60 days. The reproductive capacity of each group was assessed. Thus, in addition to histopathological analysis and the comet assay to evaluate sperm DNA deterioration, final body weight, testicular weight change, and sperm analysis were carried out. RESULTS: The findings revealed that AlCl3 caused a significant decrease in final body weight, relative weight of sex organs, sperm concentration, motility and viability, serum testosterone concentration, and a significant increase in sperm abnormalities. Furthermore, AlCl3 caused visible changes in the histological structure of the testis. CONCLUSIONS: L-carnitine treatment alleviated the harmful effects of AlCl3, as evidenced histopathologically by a noticeable improvement in testis tissues. When it comes to treating AlCl3-induced reproductive toxicity in male rat testes, L-carnitine shows promise.


Asunto(s)
Antioxidantes , Testículo , Masculino , Ratas , Animales , Cloruro de Aluminio , Antioxidantes/farmacología , Semen , Carnitina/farmacología , Peso Corporal
20.
BMC Complement Med Ther ; 24(1): 129, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521901

RESUMEN

BACKGROUND: The potent antiplasmodial activity of 1-hydroxy-5,6,7-trimethoxyxanthone (HTX), isolated from Mammea siamensis T. Anders. flowers, has previously been demonstrated in vitro. However, its in vivo activity has not been reported. Therefore, this study aimed to investigate the antimalarial activity and acute toxicity of HTX in a mouse model and to evaluate the pharmacokinetic profile of HTX following a single intraperitoneal administration. METHODS: The in vivo antimalarial activity of HTX was evaluated using a 4-day suppressive test. Mice were intraperitoneally injected with Plasmodium berghei ANKA strain and given HTX daily for 4 days. To detect acute toxicity, mice received a single dose of HTX and were observed for 14 days. Additionally, the biochemical parameters of the liver and kidney functions as well as the histopathology of liver and kidney tissues were examined. HTX pharmacokinetics after intraperitoneal administration was also investigated in a mouse model. Liquid chromatography triple quadrupole mass spectrometry was used to quantify plasma HTX and calculate pharmacokinetic parameters with the PKSolver software. RESULTS: HTX at 10 mg/kg body weight significantly suppressed parasitemia in malaria-infected mice by 74.26%. Mice treated with 3 mg/kg HTX showed 46.88% suppression, whereas mice treated with 1 mg/kg displayed 34.56% suppression. Additionally, no symptoms of acute toxicity were observed in the HTX-treated groups. There were no significant alterations in the biochemical parameters of the liver and kidney functions and no histological changes in liver or kidney tissues. Following intraperitoneal HTX administration, the pharmacokinetic profile exhibited a maximum concentration (Cmax) of 94.02 ng/mL, time to attain Cmax (Tmax) of 0.5 h, mean resident time of 14.80 h, and elimination half-life of 13.88 h. CONCLUSIONS: HTX has in vivo antimalarial properties against P. berghei infection. Acute toxicity studies of HTX did not show behavioral changes or mortality. The median lethal dose was greater than 50 mg/kg body weight. Pharmacokinetic studies showed that HTX has a long elimination half-life; hence, shortening the duration of malaria treatment may be required to minimize toxicity.


Asunto(s)
Antimaláricos , Malaria , Mammea , Ratones , Animales , Antimaláricos/toxicidad , Extractos Vegetales/toxicidad , Malaria/tratamiento farmacológico , Flores , Peso Corporal
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