Apilarnil ameliorates Bisphenol A-induced testicular toxicity in adult male rats via improving antioxidant potency and PCNA expression.

Apilarnil, a bee-derived product originating from drone larvae, offers a range of advantageous properties for both humans and animals. It functions as an antioxidant, provides neuroprotection, boosts fertility, and has antiviral capabilities. Additionally, it is a provider of androgenic hormones. These beneficial functions are supported by its chemical composition, which comprises mineral salts, vitamins, carbs, lipids, hormones, and amino acids. The current study aimed to evaluate the ameliorative effect of apilarnil against Bisphenol A (BPA)-induced testicular toxicity in male adult rats. Forty-eight Wistar albino rats were randomly classified into six groups. The first, second, and third received olive oil, BPA at a dose of 50 mg/kg body weight (bwt), and apilarnil at a dose of 0.6 g/kg bwt, respectively. The fourth, fifth, and sixth groups received apilarnil with, before, or after BPA administration, respectively. Phytochemical analysis using included linear ion trap-ultra-performance liquid chromatography-tandem mass spectrometry (LTQ-UPLC-MS/MS) and global natural products social molecular networking (GNPS) revealed the presence of lysine, 10-hydroxy-(E)-2-dodecenoic acid, apigenin7-glucoside, testosterone, progesterone, and campesterol. BPA administration decreased serum level of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, glutathione (GSH) concentration, total sperm count, motility, and vitality. Additionally, BPA increased sperm abnormalities, malondialdehyde concentration (MDA), and decreased proliferating cell nuclear antigen (PCNA) expression. The treatment with apilarnil ameliorated BPA reproductive toxicity in rats which was indicated by increased serum testosterone levels, normalized serum levels of FSH and LH, and concentration of MDA and GSH activity. Moreover, apilarnil improved sperm count, motility, morphology, and PCNA expression. Apilarnil was found to enhance reproductive hormones, MDA levels, antioxidant activity, and PCNA expression.

Enhancement potential of Moringa oleifera leaves extract on buffalo bull cryopreserved semen quality and fertilization capacity.

The aim of the present study is to evaluate the effect of Moringa oleifera leave extract (MOLE) on buffalo bull cryopreserved semen quality and fertility. Sixty ejaculates were collected from ten fertile buffalo bulls on a weekly basis for 6 weeks (n = 10 bulls & n = 60) then semen samples were pooled and divided into five groups. The semen of the control group was without additives. The semen of other groups was supplemented with MOLE at doses of 200, 400, 600 and 800 µg/ mL, respectively. One hundred thirty multiparous buffaloes were artificially inseminated with semen supplemented without or with MOLE at dose of 600 µg/ mL. Inclusion of MOLE in semen extender at dose 600 µg/ mL significantly elevated the total motility, progressive motility, membrane integrity and fertilization capacity of the post-thawed spermatozoa, as well as the total antioxidant capacity. However, it significantly decreased acrosomal defects of spermatozoa, and the concentration of malondialdehyde. This study indicated that inclusion of MOLE to semen extender improved the quality and fertility of the post-thawed buffalo bulls' semen through enhancing the activities of the antioxidant enzyme system and decreasing cryodamage of the buffalo bull spermatozoa.

Cytotoxic Potential of Novel Quinoline Derivative: 11-(1,4-Bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline against Different Cancer Cell Lines via Activation and Deactivation of the Expression of Some Proteins.

The current study evaluated the cytotoxic activity of 11-(1,4-bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline (BAPPN), a novel derivative of 5-methyl-5H-indolo[2,3-b]quinoline, against hepatocellular carcinoma (HepG2), colon carcinoma (HCT-116), breast (MCF-7), and lung (A549) cancer cell lines and the possible molecular mechanism through which it exerts its cytotoxic activity. BAPPN was synthesized and characterized with FT-IR and NMR spectroscopy. The binding affinity scores of BAPPN for caspase-3 PDB: 7JL7 was -7.836, with an RMSD of 1.483° A. In silico screening of ADME properties indicated that BAPPN showed promising oral bioavailability records in addition to their high gastrointestinal absorption and blood-brain barrier penetrability. BAPPN induced cytotoxicity, with IC50 values of 3.3, 23, 3.1, and 9.96 µg/mL against cancer cells HepG2, HCT-116, MCF-7, and A549, respectively. In addition, it induced cell injury and morphological changes in ultracellular structure, including cellular delayed activity, vanishing of membrane blebbing, microvilli, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin autophagosomes. Furthermore, BAPPN significantly increased the protein expression of caspase-3 and tumor suppressor protein (P53). However, it significantly reduced the secretion of vascular endothelial growth factor (VEGF) protein into the medium and decreased the protein expression of proliferation cellular nuclear antigen (PCNA) and Ki67 in HepG2, HCT-116, MCF-7, and A549 cells. This study indicates that BAPPN has cytotoxic action against liver, colon, breast, and lung cancer cell lines via the up-regulation of apoptotic proteins, caspase-3 and P53, and the downregulation of proliferative proteins, VEGF, PCNA, and Ki67.

Immunostimulant potential of Moringa Oleifera leaves alcoholic extract versus Oregano Essential Oil (OEO) against cyclophosphamide-induced immunosuppression in broilers chicks.

The current study was conducted to evaluate the immunoenhancement effect of Moringa oleifera leaves alcoholic extract (MOLE) versus Oregano essential oil (OEO) against cyclophosphamide induced immunosuppression in broilers chicks. A total of a three hundred one-day-old chicks were assigned randomly into three main dietary groups, control, MOLE, and OEO for 14 days. After 14 days the three main experimental groups were subdivided into six groups, control, cyclophosphamide, MOLE, MOLE and Cyclophosphamide, OEO, and OEO and cyclophosphamide. Each group of these six groups was subdivided into three subgroups. Supplementation of broiler chicks with MOLE and OEO for 14 days significantly increased body weight compared to the control group. However, injection of broiler chicks with cyclophosphamide significantly induced body weight loss, impaired immunological response represented by decreasing total leukocytic count, differential leukocytic count, phagocytic activity, phagocytic index, and hemagglutinin inhibition titer for New Castle disease virus, lymphoid organs depletion, and increased the mortality rate. In contrast, supplementation of cyclophosphamide treated chicks with MOLE and OEO significantly reduced cyclophosphamide induced body weight loss and impaired immunological responses, as it showed significant increase in body weight, total leukocytic count, differential leukocytic count, phagocytic activity, phagocytic index, and hemagglutinin inhibition titer for New Castle disease virus, lymphoid organs proliferation, and reduced the mortality rate. This study indicated that MOLE and OEO supplementation ameliorated cyclophosphamide induced body weight loss and impaired immunological responses.

Design and cytotoxic evaluation via apoptotic and antiproliferative activity for novel 11(4-aminophenylamino)neocryptolepine on hepatocellular and colorectal cancer cells.

The current study evaluated the cytotoxic activity of 11(4-Aminophenylamino)neocryptolepine (APAN), a novel derivative of neocryptolepine, on hepatocellular (HepG2) and colon (HCT-116) carcinoma cell lines as well as, the possible molecular mechanism through which it exerts its cytotoxic activity. The APAN was synthesized and characterized based on their spectral analyses. Scanning for anticancer target of APAN by Swiss software indicated that APAN had highest affinity for protein tyrosine kinase 6 enzyme. Furthermore, Super pred software indicated that APAN can be indicated in hepatic and colorectal cells with 92%. Molecular docking studies indicated that the binding affinity scores of APAN for protein PDB code: 6CZ4 of tyrosine kinase 6 recorded of - 6.6084 and RMSD value of 0.8891°A, while that for protein PDB: 7JL7 of caspase 3 was - 6.1712 and RMSD of 0.8490°A. Treatment of HepG2 and HCT-116 cells with APAN induced cytotoxicity with IC50 of 2.6 and 1.82 µg/mL respectively. In addition, it induced injury and serious morphological changes in cells including, disappearance of microvilli, membrane blebbing, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin. Moreover, APAN significantly increased protein expression of annexin V (apoptotic marker). Furthermore, APAN significantly increased protein expression of caspase 3 and P53. However, it significantly reduced secretion of VEGF protein into the medium and decreased protein expression of PCNA and Ki67 in HepG2 and HCT-116 cells. This study indicated that APAN had cytotoxic activity against HepG2 and HCT-116 cells via increasing the expression of apoptotic proteins and reducing the expression of proliferative proteins.

Ameliorative role of chitosan nanoparticles against silver nanoparticle-induced reproductive toxicity in male albino rats.

This study was designed to evaluate the protective potentials of chitosan nanoparticles (ChNPs) against silver nanoparticle (AgNP)-induced reproductive toxicity in male Wister albino rats. AgNPs, ChNPs, and AgNPs particles coated with ChNPs were characterized by using transmission electron microscope. Control rats were injected interperitoneally with 0.5% aqueous carboxymethyl cellulose. Second group was given ChNPs at a dose 300 mg/kg bwt. Third group was given AgNPs at a dose 50 mg/kg bwt. Fourth group was given AgNPs with chitosan nanoparticles simultaneously. Fifth group was given silver nanoparticles coated with chitosan nanoparticles at a dose 300 mg/kg bwt. TEM showed the formation of AgNPs with average size of 42.7 nm, ChNPs with average size of 33.3 nm, and AgNPs coated with ChNPs with average size of 48.1 nm. AgNPs significantly reduced serum levels of FSH, LH, testosterone and prolactin, sperm count, morphology index, vitality, total motility and progressive motility, the activities of catalase and superoxide dismutase, and the concentration of reduced glutathione in testicular tissues. However, it significantly increased malondialdehyde concentration in testicular tissues, sperm abnormalities, testicular tissue damages, non-progressive motility, and immotile sperms. On the contrast, ChNPs ameliorated AgNP-induced alteration in serum levels of sex hormones, spermogram, and testicular tissue's structure and functions. These results indicated that ChNPs had protective potential against AgNP-induced reproductive toxicity and ChNPs coating AgNPs had more potent protective effect than ChNPs administrated together with AgNPs.

Protective and Therapeutic Efficacy of Hesperidin versus Cisplatin against Ehrlich Ascites Carcinoma-Induced Renal Damage in Mice.

This study evaluates the antitumor efficacy of hesperidin (Hesp) versus cisplatin (Cis) in Ehrlich ascites carcinoma (EAC)-bearing mice, as well as its protective effect against Cis-triggered nephrotoxicity. Seventy female mice were allocated into control, Hesp, EAC, Hesp-protected, Hesp-treated, Cis-treated, and Cis+Hesp-treated groups. The inoculation of mice with EAC cells significantly reduced the mean survival time, while significantly increased the body weight, abdominal circumference, ascitic fluid volume, viable tumor cell count, and serum carcinoembryonic antigen, urea and creatinine levels, besides various hematological changes. Additionally, kidney tissue of EAC-bearing mice showed a significant increase in the malondialdehyde level, significant decreases in the reduced glutathione content and catalase activity, marked pathological alterations, and a strong Ki-67 expression with a weak caspase-3 expression in neoplastic cells infiltrating the renal capsule. Conversely, the administration of Hesp and/or Cis to the EAC-bearing mice induced, to various degrees, antitumor responses and alleviated the cytotoxic effects of EAC. In addition to the potent antitumor effect of the concomitant administration of Hesp and Cis, Hesp minimized the renal adverse side effects of Cis. In conclusion, Hesp may open new avenues for safe and effective cancer therapy and could be valuable for enhancing the antitumor potency and minimizing the renal adverse side effects of chemotherapeutic drugs.

Antioxidant and anti-apoptotic prophylactic effect of silymarin against lead-induced hepatorenal toxicity in rats.

This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues' malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues' architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.

Grape seed extract ameliorated Ehrlich solid tumor-induced hepatic tissue and DNA damage with reduction of PCNA and P53 protein expression in mice.

This study evaluated the ameliorative potential of grape seed extract (GSE) against Ehrlich solid tumor (EST)-induced hepatic tissue alterations in mice. The control group was infused with physiological saline. The second group received GSE (50 mg/kg day by day orally) for 2 weeks. The third group was subcutaneously injected with 2.5 million of EST cells. The fourth group was injected with EST cells and treated with GSE extract simultaneously. The fifth group was injected with EST cells and kept for 2 weeks until the appearance of a solid tumor, then treated with GSE for 2 weeks. The phytochemical analysis of GSE revealed the presence of total phenols (17.442 mg GAE/g) and total flavonoid (6.687 mg CE/g) with antioxidant activity of 81.506 mg TE/g DPPH. The Ehrlich solid tumor significantly raised the activities of ALT, AST, and ALP; the level of alpha fetoprotein (AFP) in serum; and the protein expressions of hepatic proliferating cell nuclear antigen (PCNA) and tumor suppressor protein (P53), as well as induced DNA damage and pathological alterations in liver tissue. However, it significantly reduced serum albumin and total protein levels. In contrast, the co- or post-treatment of EST-bearing mice with GSE reduced the activities of ALT, AST, and ALP; the level AFP in serum; and hepatic P53 and PCNA protein expressions. In addition, it reduced EST-induced hepatic DNA damage and pathological alterations, while it increased serum albumin and total protein levels. This study suggested that GSE is a potent hepatoprotective agent and both co- and post-treatment of EST-bearing mice with GSE almost had the same effects.

Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma-induced hepatorenal injury in mice.

Ehrlich ascites carcinoma induces hepatorenal injuries while acridine derivatives have antioxidant, anticancer, and anti-inflammatory. Thus, this study evaluated the protective potential of a newly synthesized the 9-diaminoacridine derivative (9-DAAD), N1-(acridin-9-yl) propane-1, 3-diamine hydrochloride, against Ehrlich ascites carcinoma (EAC) induced hepatorenal injury in female mice. Forty female mice were allocated into 4 groups. Group I was injected with 0.1% DMSO subcutaneously and kept a control. Group II received 9-DAAD (30 mg/kg bw/2 days) subcutaneously for 2 weeks. Group III was injected interaperitonealy with 2.5 × 106 cells of EAC/20 g bw. Group IV was injected with EAC as the third group and administered with 9-DAAD as the second group for 2 weeks after induction of EAC. EAC significantly elevated total leukocytes and platelets counts; activities of serum AST, ALT, and ALP; serum levels of alpha-fetoprotein; carcinoembryonic antigen; urea and creatinine; and expression of vascular endothelial growth factor protein in hepatic and renal tissues. Meanwhile it decreased red blood cells count, hemoglobin concentration and hematocrit value. At the same time, it significantly reduced serum levels of total protein and albumin and altered hepatic and renal tissues structures. Also, EAC decreased apoptosis and DNA synthesis in hepatic and renal cells. However, treatment of EAC-bearing mice with 9-DAAD improved liver and kidney structures, functions and modulated EAC altered parameters, as well as it reduced hepatic and renal cells proliferation and DNA synthesis. This study indicated that 9-DAAD had a potential ameliorative effect against EAC-induced hepatorenal injury.

Ginseng attenuates fipronil-induced hepatorenal toxicity via its antioxidant, anti-apoptotic, and anti-inflammatory activities in rats.

Fipronil (FPN) is a relatively new and broad spectrum insecticide that induces toxic effects to animals and humans through induction of oxidative stress. Ginseng is a medicinal plant that has antioxidant, anti-inflammatory, and anti-apoptotic activities. Thus, the current study was conducted to evaluate the anti-toxic potential of ginseng aqueous extract (GAE) against FPN-induced hepatorenal toxicity in rats. Thirty-two male Wistar albino rats were randomly allocated into four equal groups. Rats of the control group received distilled water. The second group was administrated with GAE at a dose of 200 mg/kg b.w. orally day by day for 6 weeks. The third group was intoxicated with FPN at a dose of 4.85 mg/kg b.w. orally day by day for 6 weeks. The fourth group was administrated with GAE 2 h before FPN intoxication. Intoxication of rats with FPN significantly elevated the activities of serum alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine, as well as increased malondialdehyde level and protein expressions of caspase-3 and cyclooxygenase-2 in hepatic and renal tissues. However, it significantly decreased hepatic and renal GSH content and catalase activity. In addition, it induced histopathological alterations in hepatic and renal tissue architectures. Conversely, concomitant oral administration of GAE ameliorated the FPN-induced biochemical, pathological, and histochemical alterations in both hepatic and renal tissues. This study indicated that ginseng attenuates FPN-induced hepatorenal toxicity, possibly via its antioxidant, anti-apoptotic, and anti-inflammatory properties. Graphical Abstract CAL ABSTRACTPHIRAG.

Fucoidan Ameliorates Oxidative Stress, Inflammation, DNA Damage, and Hepatorenal Injuries in Diabetic Rats Intoxicated with Aflatoxin B1.

The current study was carried out to evaluate the ameliorative effect of fucoidan against aflatoxicosis-induced hepatorenal toxicity in streptozotocin-induced diabetic rats. Sixty-four Wister albino male rats were randomly assigned into eight groups (8 rats each) that received normal saline, fucoidan (FUC) at 100 mg/kg/day orally for 4 weeks, streptozotocin (STZ) at 50 mg/kg/i.p. single dose, STZ plus FUC, aflatoxin B1 (AFB1) at 50 µg/kg/i.p. after one month of the beginning of the experiment for 2 weeks, AFB1 plus FUC, STZ plus AFB1, or STZ plus AFB1 and FUC. Injection of rats with STZ induced hyperglycemia. Rats with STZ-induced diabetes, with or without AFB1 intoxication, had significantly elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of serum urea, creatinine, cholesterol, 8-oxo-2'-deoxyguanosine, interleukin-1ß, interleukin-6, and tumor necrosis factor-α. In addition, these rats exhibited increased lipid peroxidation and reduced glutathione concentration and activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes in the hepatic and renal tissues. In contrast, administration of FUC to diabetic rats, with or without AFB1 intoxication, ameliorated the altered serum parameters, reduced oxidative stress, DNA damage, and inflammatory biomarkers, and enhanced the antioxidant defense system in the hepatic and renal tissues. These results indicated that FUC ameliorated diabetes and AFB1-induced hepatorenal injuries through alleviating oxidative stress, DNA damage, and inflammation.

Allicin modulates diclofenac sodium induced hepatonephro toxicity in rats via reducing oxidative stress and caspase 3 protein expression.

PURPOSE: This study was designed to evaluate the protective effects of allicin against diclofenac sodium induced hepatonephro toxicity in rats. METHODS: Sixty male Wister albino rats were assigned into six groups. The control group received calcium carbonate and corn starch. 2nd group received diclofenac sodium (2 mg/kg bw orally) for 30 days. 3rd group received allicin (45 mg/kg bw orally) for 30 days. 4th group administrated diclofenac sodium as in the 2nd group and allicin (15 mg/kg bw orally) for 30 days. 5th group received diclofenac sodium as in the 2nd group and allicin (30 mg/kg bw orally) for 30 days. 6th group received diclofenac sodium as 2nd and allicin (45 mg/kg bw orally) for 30 days. RESULTS: Diclofenac sodium significantly elevated activities of serum aspartate aminotransferase and alanine aminotransferase and serum levels of creatinine and urea. In addition, it induced hyperglycemia, lipid peroxidation, pathological alteration and caspase 3 protein expression in hepatic and renal tissues. However, it decreased reduced glutathione concentration and proliferating cell nuclear antigen protein expression in hepatic tissues. In contrast, allicin modulated the diclofenac sodium induced alteration in liver and kidney functions and structures dose dependently. CONCLUSION: This study indicated that allicin had potential preventive effects against diclofenac sodium induced hepatonephro toxicity in rats.

Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice.

The current study was carried out to evaluate the protective effect of grape seed proanthocyanidins extract (GSPE) against Ehrlich solid tumor (EST) induced renal injury, with the respect to DNA fragmentation and P53 and PCNA proteins expression in renal tissue. A total of 50 female mice were randomly assigned into five groups. Control mice were injected with physiological saline solution. Mice of the 2nd group were administered with GSPE (50 mg/kg bw/every 2day/per OS) for 2 weeks and injected with physiological saline solution. Mice of the 3rd group were injected subcutaneously with 2.5 million cells of EAC/mouse. Mice of the 4th group were injected with EAC as the 3rd group and administered with GSPE as the 2nd group simultaneously for 2 weeks. Mice of the 5th group were injected with EAC as the 3rd group and left for 2 weeks (till development of solid tumor), then treated with GSPE for another 2 weeks. EST significantly increased serum levels of urea, creatinine, potassium and chloride. In addition, it induced renal tissue and DNA injuries and increased P53, PCNA and ki67 proteins expression in renal tissues. On the other hand, it decreased serum levels of sodium and calcium ions. However, treatment of EST bearing mice with GSPE normalized serum levels of the above-mentioned parameters and improved renal tissue structure and reduced renal tissue DNA damage and P53, PCNA and ki67 proteins expression. These results indicated that GSPE is a promising nephron protective agent against EST induced renal injury.

Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon-induced reproductive toxicity in male rats.

This study was designed to evaluate protective effect of Saussurea lappa root aqueous extract against Ethephon (2-chloroethylphosphonic acid)-induced reproductive toxicity in rats. Control group received distilled water. Second group was given S. lappa extract at a dose 50 mg/kg bw. Third group was given Ethephon at a dose 200 mg/kg bw. Fourth, fifth, and sixth groups were given S. lappa extract before, with or after Ethephon administration, respectively. Ethephon intoxication significantly decreased serum levels of follicle stimulating hormone, luteinizing hormone, testosterone, and prolactin. Also, it significantly decreased sperms count, vitality, morphology index, total motility, progressive motility, and proliferating cell nuclear antigen protein expressions in spermatogonia. However, it significantly increased sperms abnormalities, testicular tissue and DNA damages, P53 protein expressions, noprogressive motility, and immotile sperms. In contrast, S. lappa extract ameliorated these alterations. These results indicated that S. lappa had potential preventive and curative effects against Ethephon-induced reproductive toxicity in rats.

l-Carnitine-induced amelioration of HFD-induced hepatic dysfunction is accompanied by a reduction in hepatic TNF-α and TGF-ß1.

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-ß1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-ß1.

Progesterone dose-dependently modulates hepatocyte growth factor production in 3T3-L1 mouse preadipocytes.

It is well documented that estrogen is predominant inducer of hepatocyte growth factor (HGF) in a variety of cell types. However, the effect of progesterone (P) remains to be elusive. Thus, in the present study, we examined the effect of P and combined effect of P and 17ß-estradiol (E2) on HGF expression and production in 3T3-L1 fibroblastic preadipocytes and mature adipocytes, as a model of stromal cells. Northern blot analysis showed that hgf mRNA expressed in preadipocytes was notably higher than that of mature adipocytes, and increased by treatment of preadipocytes with E2 or 10 nM P, but not with 1,000 nM P. The E2-induced hgf mRNA expression was enhanced by 10 nM P, but suppressed by 1,000 nM P. Western blot analysis revealed that biological active forms of HGF protein was found in the preadipocyte culture medium, while the lesser amount of HGF precursor protein was detected in the mature adipocyte culture medium. The amounts of HGF were changed dependently on the hgf mRNA expression levels. These results indicate that HGF production is intricately regulated by E2 and P at the transcriptional levels in 3T3-L1 cells, and may explain the changes in the HGF production during the mammary gland development, especially decrease in HGF expression during pregnancy when P concentration is high.

Retinoic acid modulates lipid accumulation glucose concentration dependently through inverse regulation of SREBP-1 expression in 3T3L1 adipocytes.

It is well known that retinoic acid (RA) suppresses adipogenesis, although there are some contradicting reports. In this study, we examined the effect of extracellular glucose on RA-induced suppression of adipogenesis in 3T3L1 cell culture. When the cells were cultured in normal glucose medium (NG), the addition of RA suppressed lipid accumulation. However, when cultured in high glucose medium (HG), addition of RA to the cells enhanced lipid accumulation. These changes were accompanied by parallel alterations in fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1 gene expression. Transfection of SREBP-1 siRNA suppressed RA-induced enhancement of lipid accumulation and FAS expression in the cells cultured with HG. Transfection of the nuclear form of SREBP-1a cDNA into the cells cultured with NG inhibited RA-induced suppression of lipid accumulation and FAS expression. Moreover, RA- and HG-induced SREBP-1a expression occurred at the early phase of adipogenesis and was dependent on glucocorticoid to induce liver X receptor (LXR) ß, peroxisomal proliferator-activated receptor (PPAR) γ and retinoid X receptor (RXR), the key nuclear factors influencing the SREBP-1a gene expression. These results suggest that RA suppresses and enhances lipid accumulation through extracellular glucose concentration-dependent modulation of SREBP-1 expression.

An aqueous extract from Moringa oleifera leaves ameliorates hepatotoxicity in alloxan-induced diabetic rats.

This study was carried out to evaluate the possible mechanisms through which an aqueous extract from MO leaves demonstrates hepatoprotective effects in alloxan-induced diabetic rats. Eighty albino rats were assigned to 4 groups. The control group was orally administered sterile saline. The second group was injected with alloxan (150 mg/kg body mass (b.m.)) by intraperitoneal injection (i.p.). The third group was given MO (250 mg/kg b.m.) orally, daily. The fourth group was injected with alloxan, as for the second group, and administrated an aqueous extract of MO leaves, as for the third group. Alloxan induced degenerative changes in hepatic and pancreatic tissues, increased hepatic lipid peroxidation, and increased gene expression of PC and caspase 3. However, it decreased the activities of hepatic SOD and CAT, and gene expression of GS. In contrast, the MO extract prevented changes to the histoarchitecture of hepatic and pancreatic tissues and normalized the reduced hepatic levels of glutathione, as well as the activities of SOD and CAT, and the gene expression of GS, while reducing blood glucose levels, hepatic lipid peroxidation, and the gene expression of PC and caspase 3. This study indicated that an aqueous extract of MO leaves can be a potent antioxidant and used as an hepatoprotective agent.

Moringa oleifera leaf extract ameliorates alloxan-induced diabetes in rats by regeneration of ß cells and reduction of pyruvate carboxylase expression.

Moringa oleifera Lam. contains many active ingredients with nutritional and medicinal values. It is commonly used in folk medicine as an antidiabetic agent. The present study was designed to investigate how an aqueous extract from the leaves of M. oleifera reveals hypoglycemia in diabetic rats. M. oleifera leaf extract counteracted the alloxan-induced diabetic effects in rats as it normalized the elevated serum levels of glucose, triglycerides, cholesterol, and malondialdehyde, and normalized mRNA expression of the gluconeogenic enzyme pyruvate carboxylase in hepatic tissues. It also increased live body weight gain and normalized the reduced mRNA expression of fatty acid synthase in the liver of diabetic rats. Moreover, it restored the normal histological structure of the liver and pancreas damaged by alloxan in diabetic rats. This study revealed that the aqueous extract of M. oleifera leaves possesses potent hypoglycemic effects through the normalization of elevated hepatic pyruvate carboxylase enzyme and regeneration of damaged hepatocytes and pancreatic ß cells via its antioxidant properties.