Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis.

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.

Ameliorative effects of propolis and wheat germ oil on acute toxoplasmosis in experimentally infected mice are associated with reduction in parasite burden and restoration of histopathological changes in the brain, uterus, and kidney.

Toxoplasmosis continues to be a prevalent parasitic zoonosis with a global distribution. This disease is caused by an intracellular parasite known as Toxoplasma gondii, and the development of effective novel drug targets to combat it is imperative. There is limited information available on the potential advantages of wheat germ oil (WGO) and propolis, both individually and in combination, against the acute phase of toxoplasmosis. In this study, acute toxoplasmosis was induced in Swiss albino mice, followed by the treatment of infected animals with WGO and propolis, either separately or in combination. After 10 days of experimental infection and treatment, mice from all groups were sacrificed, and their brains, uteri, and kidneys were excised for histopathological assessment. Additionally, the average parasite load in the brain was determined through parasitological assessment, and quantification of the parasite was performed using Real-Time Polymerase Chain Reaction targeting gene amplification. Remarkably, the study found that treating infected animals with wheat germ oil and propolis significantly reduced the parasite load compared to the control group that was infected but not treated. Moreover, the group treated with a combination of wheat germ oil and propolis exhibited a markedly greater reduction in parasitic load compared to the other groups. Similarly, the combination treatment effectively restored the histopathological changes observed in the brain, uterus, and kidney, and the scoring of these reported lesions confirmed these findings. In summary, the present results reveal intriguing insights into the potential therapeutic benefits of wheat germ oil and propolis in the treatment of acute toxoplasmosis.

Comprehensive Tools of Alkaloid/Volatile Compounds-Metabolomics and DNA Profiles: Bioassay-Role-Guided Differentiation Process of Six Annona sp. Grown in Egypt as Anticancer Therapy.

Trees of the Annona species that grow in the tropics and subtropics contain compounds that are highly valuable for pharmacological research and medication development and have anticancer, antioxidant, and migratory properties. Metabolomics was used to functionally characterize natural products and to distinguish differences between varieties. Natural products are therefore bioactive-marked and highly respected in the field of drug innovation. Our study aimed to evaluate the interrelationships among six Annona species. By utilizing six Start Codon Targeted (SCoT) and six Inter Simple Sequence Repeat (ISSR) primers for DNA fingerprinting, we discovered polymorphism percentages of 45.16 and 35.29%, respectively. The comparison of the profiles of 78 distinct volatile oil compounds in six Annona species was accomplished through the utilization of GC-MS-based plant metabolomics. Additionally, the differentiation process of 74 characterized alkaloid compound metabolomics was conducted through a structural analysis using HPLC-ESI-MSn and UPLC-HESI-MS/MS, and antiproliferative activities were assessed on five in vitro cell lines. High-throughput, low-sensitivity LC/MS-based metabolomics has facilitated comprehensive examinations of alterations in secondary metabolites through the utilization of bioassay-guided differentiation processes. This has been accomplished by employing twenty-four extracts derived from six distinct Annona species, which were subjected to in vitro evaluation. The primary objective of this evaluation was to investigate the IC50 profile as well as the antioxidant and migration activities. It should be noted, however, that these investigations were exclusively conducted utilizing the most potent extracts. These extracts were thoroughly examined on both the HepG2 and Caco cell lines to elucidate their potential anticancer effects. In vitro tests on cell cultures showed a significant concentration cytotoxic effect on all cell lines (HepG2, HCT, Caco, Mcf-7, and T47D) treated with six essential oil samples at the exposure time (48 h). Therefore, they showed remarkable antioxidant activity with simultaneous cytotoxic effects. In total, 50% and 80% of the A. muricata extract, the extract with the highest migratory activity, demonstrated a dose-dependent inhibition of migration. It was strong on highly metastatic Caco cells 48 h after treatment and scraping the Caco cell sheet, with the best reduction in the migration of HepG2 cells caused by the 50% A. reticulata extract. Also, the samples showing a significant IC50 value showed a significant effect in stopping metastasis and invasion of various cancer cell lines, making them an interesting topic for further research.

High Prevalence of Bovine Cardiac Cysticercosis in Upper Egypt: An Epidemiological and Histopathological Study.

Bovine cysticercosis is categorized as a serious parasitic zoonotic infestation. The infection is mainly caused by the tapeworm Taenia saginata, which infects cattle and humans. The larval stage, Cysticercus bovis (C. bovis), is found in the skeletal and cardiac muscles of infected cattle. Despite its potential public health concern, few studies have been conducted on cardiac cysticercosis in Upper Egypt. This study investigates the prevalence, epidemiology, and impact of cardiac cysticercosis in Upper Egypt, emphasizing how histopathological changes in cardiac muscle and physiological parameters might be associated with the infection. From December 2022 to October 2023, a total of 941 animals from Assiut province, Upper Egypt, were slaughtered and their cardiac muscles were examined for the presence of C. bovis. Cysts were classified as viable or degenerated through macroscopic inspection. The overall prevalence of C. bovis infected hearts made up 10.8% of the total examined. The highest prevalence rate was in the summer season followed by spring; winter had the lowest infections. The histopathological examination of infected tissues revealed immune cell infiltration around Cysticercus-infected areas. Additionally, Bax immunostaining demonstrated the apoptotic effect of cysticercosis. Regarding the measured physiological parameters, there were non-significant changes in plasma levels of total protein and albumin in cattle infected with cysticercosis compared with control animals. Moreover, there was a significant decrease in total antioxidant capacity (TAC) combined with a significant increase in lipid peroxide (Malondialdehyde) (MDA), troponin T, and lactate dehydrogenase (LDH) activity in infected animals. The present work documented a set of epidemiological and pathological findings, revealing that C. bovis is a potentially harmful parasite and can cause significant health problems in both cattle and humans.

Molluscicidal activity of sodium hypochlorite against Biomphlaria alexandrina snails: Immunological and hepato-endocrine alterations with in silico docking study.

Schistosomiasis is a tropical disease that widely neglected. Schistosoma mansoni reproduce asexually within the freshwater snail, Biomphlaria alexandrina. Sodium hypochlorite (NaOCl) is a widely used disinfectant, so its effect against gainst B. alexandrina snails was evaluated. The present results showed that NaOCl has a molluscicidal activity against adult B. alexandrina snails at LC50 1.25 ppm. Hemocytes displayed varied morphological forms after being exposed to the LC10 and LC25 concentrations of NaOCl in B. alexandrina snails, and the phagocytic index of B. alexandrina snail's hemocytes significantly increased. The phagocytic potency of exposed hemocytes to charcoal showed ruptured plasma membrane, engulfed particles, vacuolation in the cytoplasm and degeneration of nuclei. When B. alexandrina snails were treated with sublethal concentrations of NaOCl, transaminases (AST & ALT), alkaline and acid phosphatase activities were significantly increased. In contrast, the total protein, albumin concentrations, Testosterone (T) and 17ß Estradiol (E) showed a significant decrease (p ≤ 0.05) as compared to the control groups. The molecular docking interaction showed high efficiency for the ligand, NaOCl against the receptor binding sites of the acid phosphatase, alanine aminotransferase, estrogen and testosterone. The present results showed that NaOCl could be used as an effective molluscicide against B. alexandrina snails but more attention should be paid to investigate the side effects on the non-target organisms living in the freshwater environment.

Neuro-amelioration of Ficus lyrata (fiddle-leaf fig) extract conjugated with selenium nanoparticles against aluminium toxicity in rat brain: relevance to neurotransmitters, oxidative, inflammatory, and apoptotic events.

Aluminium is a non-essential metal, and its accumulation in the brain is linked with potent neurotoxic action and the development of many neurological diseases. This investigation, therefore, intended to examine the antagonistic efficacy of Ficus lyrata (fiddle-leaf fig) extract (FLE) conjugated with selenium nanoparticles (FLE-SeNPs) against aluminium chloride (AlCl3)-induced hippocampal injury in rats. Rats were allocated to five groups: control, FLE, AlCl3 (100 mg/kg), AlCl3 + FLE (100 mg/kg), and AlCl3 + FLE-SeNPs (0.5 mg/kg). All agents were administered orally every day for 42 days. The result revealed that pre-treated rats with FLE-SeNPs showed markedly lower acetylcholinesterase and Na+/K+-ATPase activities in the hippocampus than those in AlCl3 group. Additionally, FLE-SeNPs counteracted the oxidant stress-mediated by AlCl3 by increasing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents in rat hippocampus. Besides, the formulated nanoparticles decreased the hippocampal malondialdehyde, carbonyl protein, and nitric oxide levels of AlCl3-exposed animals. Furthermore, FLE-SeNPs attenuated neural tissue inflammation, as demonstrated by decreased interleukin-1 beta, interleukin-6, nuclear factor kappa B, and glial fibrillary acidic protein. Remarkable anti-apoptotic action was exerted by FLE-SeNPs by increasing B cell lymphoma 2 and decreasing caspase-3 and Bcl-2-associated-X protein in AlCl3-exposed rats. The abovementioned results correlated well with the hippocampal histopathological findings. Given these results, SeNPs synthesized with FLE imparted a remarkable neuroprotective action against AlCl3-induced neurotoxicity by reversing oxidative damage, neuronal inflammation, and apoptosis in exposed rats.

Parasitological, Molecular, and Histopathological Investigation of the Potential Activity of Propolis and Wheat Germ Oil against Acute Toxoplasmosis in Mice.

Toxoplasmosis is one of the most common parasitic zoonoses that affects all vertebrates. The drugs most commonly used against toxoplasmosis have many side effects, making the development of new antiparasitic drugs a big challenge. The present study evaluated the therapeutic effectiveness of novel herbal treatments, including propolis and wheat germ oil (WGO), against acute toxoplasmosis. A total of 50 albino mice were divided into five groups: group 1 (G1) (non-infected and non-treated); group 2 (G2) (infected without treatment); group 3 (G3) (treated with propolis); group 4 (G4) (treated with WGO); group 5 (G5) (treated with a combination of propolis and WGO). The effects of the herbal substances on different organs, mainly liver, spleen, and lungs, were investigated using parasitological, molecular, and histopathological examinations. The results of parasitological examination demonstrated statistically significant (p < 0.05) differences in the parasitic load between treated groups (G3, G4, and G5) compared to the control positive group (G2). These differences were represented by a significant reduction in the parasite load in stained tissue smears from the liver obtained from the animals treated with propolis (G3) compared to the parasite load in the positive control group. Similarly, animals (G4) treated with WGO exhibited a significant reduction in the parasite load versus the positive control group, while the lowest parasite load was found in G5, treated with propolis and WGO. Quantification of the parasite burden through molecular methods (PCR) revealed similar findings represented by reduction in the parasite burden in all treated groups with WGO and propolis as compared to the control group. Importantly, these previous parasitological and molecular findings were accompanied by a marked improvement in the histopathological picture of the liver, spleen, and lungs. In conclusion, propolis and WGO showed a good combination of therapeutic efficacy against acute toxoplasmosis.

Insights into HPLC-MS/MS Analysis, Antioxidant and Cytotoxic Activity of Astragalus fruticosus against Different Types of Cancer Cell Lines.

Plants from the genus Astragalus are gaining attention for their pharmacological importance. However, the information available regarding the HPLC-MS/MS chemical profile of A. fruticosus is inadequate. In this study, we performed HPLC-MS/MS analysis using electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). We tentatively identified 11 compounds in the A. fruticosus methanolic extract, including five flavonoidal and six saponin glycosides. The extract showed moderate antioxidant activity with 21.05% reduction in DPPH UV absorption. The preliminary cytotoxic screening against seven human cancer cell lines using 100 µg/mL extract showed prominent cytotoxic potential against colorectal cancer HCT-116 with 3.368% cell viability. It also showed moderate cytotoxic potential against prostate (DU-145), ovarian (SKOV-3) and lung (A-549) cancer cell lines with cell viability of 14.25%, 16.02% and 27.24%, respectively. The IC50 of the total extract against HCT-116 and DU-145 cell lines were 7.81 µg/mL and 40.79 µg/mL, respectively. The observed cytotoxicity of the total methanolic extract from the leaves against colorectal cancer might facilitate future investigations on cytotoxic agent(s) for disease management.

Wheat Germ Oil and Propolis Decrease Parasite Burden and Restore Marked Histopathological Changes in Liver and Lung in Mice with Chronic Toxoplasmosis.

Toxoplasmosis is a parasitic zoonotic disease with a worldwide distribution. Its effects can be critical in immunocompromised patients. However, there is a limited availability of effective, low-toxicity drugs against this disease, particularly in its chronic form. The present study evaluated the effect of propolis and wheat germ oil (WGO) as safe, natural products to reduce Toxoplasma cysts in experimentally infected mice. For the experiment, five groups (10 mice per group) were examined: Group 1: negative control (noninfected, nontreated); Group 2: positive control (infected, nontreated); Group 3: infected and treated with WGO at a dose of 0.2 mg/1.5 mL per kg body weight/day; Group 4: infected and treated with 0.1 mL propolis extract/day; and Group 5: infected and treated with a combination of WGO and propolis at the same doses as Group 3 and 4. After the mice were sacrificed, liver and lung specimens underwent histopathological examination, and the parasite burden was investigated by parasitological methods and quantified using real-time polymerase chain reaction. Notably, the results showed a substantial decrease in parasitic burden in Group 5 compared to the control group. These results were further confirmed by molecular analysis and quantification of the DNA concentration of the Toxoplasma P29 gene after treatment in all tested samples. Furthermore, the combination of propolis and WGO restored all histopathological changes in the liver and lungs. Taken together, these findings provide remarkably promising evidence of the effects of the combination of WGO and propolis against chronic toxoplasmosis in mice.

Evaluation of the antineoplastic property of prodigiosins and 5-fluorouracil in restraining the growth of Ehrlich solid tumors in mice.

Prodigiosins have been shown to have anticancer activities. 5-Fluorouracil (5-FU) is broadly used chemotherapeutic drug that treats different solid tumors including breast cancer but has low response rates and a variety of side effects. In this study, we evaluated the anticancer properties of prodigiosins in a murine model "Ehrlich tumor" and tested whether it can be added to 5-FU to potentiate its effects. Markers of oxidative stress; MDA, NO, and GSH levels were evaluated as well as antioxidant enzyme activities of CAT SOD, GR, and GPx. The levels of Bax, Bcl-2, PCNA, and NF-κB proteins were measured using ELISA kits. The mRNAs of p53 and Cdc2 and Casp3 were quantitatively measured by real-time PCR and ELISA respectively. Cell cycle analysis was performed using flow cytometery. Prodigiosins did not influence tumor volume. Prodigiosins have not induced oxidative stress while 5-FU did increase MDA, NO but decreased GSH levels. The combination prodigiosins and 5-FU did reduce oxidative stress markers; MDA, NO and increased GSH levels. Prodigiosins significantly increased CAT only while 5-FU did decreased SOD, CAT, GPx, and GR. The combination prodigiosins and 5-FU increased the levels of these enzymes again. Prodigiosins increased the Bax/Bcl-2 ratio while the combination deceased it. In conclusion, prodigiosins have pronounced anticancer properties but their combination with 5-FU decreased oxidative stress exerted by 5-FU but weakened the apoptotic effects of 5-FU. Prodigiosins could affect a key mechanism through which 5-FU exerts its tumor inhibitory effects.

Effect of mesenchymal stem cells on cytochrome-c release and inflammation in colon cancer induced by 1,2-dimethylhydrazine in Wistar albino rats.

Colon cancer is one of the most common causes of deaths by cancer worldwide. Stem cells have immunosuppressive properties that promote tumor targeting and circumvent obstacles currently in gene therapy. Bone marrow stem cells are believed to have anticancer potential. The transplantation of mesenchymal stem cells (MSCs), a type of bone marrow stem cells, has been considered a potential therapy for patients with solid tumors due to their capability to enhance the immune response; MSC transplantation has received renewed interest in recent years. The present study aimed to evaluate the antiapoptotic effects of the MSCs on 1,2-dimethylhydrazine (DMH)-induced inflammation in the rat model of colorectal cancer. The rats were randomly allocated into four groups: control, treated with MSCs, induced by DMH, and induced by DMH and treated with MSCs. The MSCs were intra-rectally injected, and DMH was subcutaneously injected at 20 mg/kg body weight once a week for 15 weeks. The administration of MSCs into rats starting from day 0 of the DMH injection was found to enhance the histopathological picture. The MSC treatment resulted in fewer inflammatory cells than in the DMH group. Therefore, our findings suggest that BMCs have antitumor effects by modulating the cellular redox status and down-regulating the pro-inflammatory genes. Thus, BMCs may provide therapeutic value for colon cancer treatment.

A rapid and simple single-step method for the purification of Toxoplasma gondii tachyzoites and bradyzoites.

This study describes a simple method for the large-scale isolation of pure Toxoplasma gondii tachyzoites and bradyzoites. T. gondii tachyzoites were obtained from infected human foreskin fibroblasts (HFFs) and peritoneal exudates of mice, while tissue cysts containing bradyzoites were collected from chronically infected mice. Harvested cells and brain tissues were incubated in Hanks balanced salt solution (HBSS), containing 0.25% trypsin and 0.5% taurodeoxycholic acid (TDC) for 5 min. Subsequent washes in phosphate buffered saline (PBS) were conducted, and the cell viability of the preparations was good, as determined by flow cytometry and ability to reinfect HFF cells and propagate in mice. The purification procedure allowed for a rapid preparation of pure T. gondii tachyzoites and bradyzoites in sufficient quantity that can be used for downstream procedures. The advantage of the new method is that it is convenient and inexpensive.

A preliminary study of cytokine gene polymorphism effects on Saudi patients with colorectal cancer.

OBJECTIVE:  To determine the possible associations of polymorphisms in interleukin (IL)-8 (rs4073 T/A), IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G and rs2227485 C/T), IL-27 (rs17855750 T/G), and transforming growth factor beta 1 (TGFß1) (rs1800469 C/T) with colorectal cancer (CRC) susceptibility in Saudi patients. METHODS: The case-control study was carried out between July 2019 and January 2020 in King Khaled University Hospital, Riyadh, Saudi Arabia. A total of 70 patients with CRC and 70 healthy controls were included  in  the  study.  Single nucleotide polymorphisms of promoter regions were determined using TaqMan genotyping assays. RESULTS:  A statistically significant reduction in CRC risk was identified for carriers of the IL-10 (rs1800896 A/G) AG genotype, IL-22 (rs1179251 C/G) G allele, IL-27 (rs17855750 T/G) G allele and TGFß1 (rs1800469 C/T) CT and TT genotype. While IL-10 (rs1800896 A/G) AA genotype and TGFß1 (rs1800469 C/T) CC genotype were significantly associated with increased susceptibility to CRC. No significant associations were identified between the cytokine polymorphisms of IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T), and CRC risk. Conclusion: Our findings indicate a significant impact of IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G), IL-27 (rs17855750 T/G) and TGF-ß1 (rs1800469 C/T) polymorphisms on risk of CRC; while the IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T) and polymorphisms were not associated with CRC risk.

The Effects of Silver Nanoparticles Biosynthesized Using Fig and Olive Extracts on Cutaneous leishmaniasis Induced Inflammation in Female Balb/c Mice.

Leishmaniasis is a group of infectious and non-contagious severe parasitic diseases, caused by protozoans of the Leishmania genus. Natural products characterize a rich source of prospective chemical entities for the development of new effective drugs for neglected diseases. Scientific evaluation of medicinal plants has made it possible to use some metabolites from flavonoids and polyphenols compounds for the treatment of parasitic diseases. Therefore, we aimed in this study to evaluate the protective effect of Silver nanoparticles (Ag-NPs) biosynthesized using Fig and Olive extracts (NFO) against Cutaneous leishmaniasis in female Balb/c mice. A total of 70 mice were used and divided into seven groups. Treatment was initiated when local lesions were apparent, we found Fig and Olive extracts were found to be a good source for the synthesis of (Ag-NPs), their formation was confirmed by color change and stability in solution. Nanoparticles biosynthesized using Fig and Olive extracts induced a reduction in the average size of cutaneous leishmaniasis lesions compared with the untreated mice. Moreover, nanoparticles treatment decreased oxidative stress (LPO, NO), down regulation gene expression levels (TNF-α, IL-1ß and BAX) and this antileishmanial activity of nanoparticles was associated with enhanced antioxidant enzyme activities. In addition, histopathological evaluation proved the antileishmanial activity of nanoparticles compared to the positive control. Therefore, we aimed in this study to evaluate the protective effect of silver nanoparticles biosynthesized using Fig and Olive extracts against cutaneous lesions induced by Leishmania major infection through their anti-inflammatory, antioxidant activities and faster clinical efficacy than standard pentavalent antimonial treatment.

Green Coffea arabica Extract Ameliorates Testicular Injury in High-Fat Diet/Streptozotocin-Induced Diabetes in Rats.

Diabetes mellitus (DM) is a chronic endocrine disease characterized by persistent hyperglycemia. Oxidative damage, inflammatory cytokines, and apoptotic cell death play a major role in the induction and progression of male testicular damage. Plant-derived phytochemicals such as green coffee (Coffea arabica) can possess antidiabetic effects with little toxicity. The current study is aimed at investigating the therapeutic roles of green coffee in diabetic testicular injury stimulated by high-fat diet/streptozotocin administration. Diabetes mellitus was induced by a high-fat diet and a single dose of streptozotocin (STZ) (35 mg kg-1) in male albino rats. Diabetic animals were orally given two different concentrations of green coffee (50 mg kg-1 and 100 mg kg-1) for 28 days. The levels of testosterone, luteinizing hormone, and follicle-stimulating hormone and parameters of oxidative stress, inflammation, and apoptosis were measured. mRNAs and protein levels were detected quantitatively by real-time PCR and ELISA, respectively. In the diabetic group, the levels of testosterone, luteinizing hormone, and follicle-stimulating hormone showed a significant reduction while they increased significantly after green coffee treatment. A significant increase of antioxidant markers glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase along with decreased levels of lipid peroxides and nitric oxide was observed after green coffee treatment in the diabetic group. Finally, the levels of IL-1ß, TNF-α, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group. We conclude that testicular oxidative impairment induced by a high-fat diet (HFD) and STZ can be reversed by green coffee. Administration of green coffee could represent a promising therapeutic agent which can help the treatment of type 2 DM-induced testicular dysfunction.

Nephroprotective effects of chlorogenic acid against sodium arsenite-induced oxidative stress, inflammation, and apoptosis.

BACKGROUND: Chronic exposure to arsenic (As) leads to serious renal disorders. Chlorogenic acid (CGA), a phenolic compound, has several well known physiological benefits, including antioxidant and anti-inflammatory activities. The present study investigated the potential renoprotective effects of CGA on sodium arsenite (NaAsO2 )-induced kidney damage in mice. The mice were randomly allocated into five groups to receive daily treatment with CGA (200 mg kg-1 ), NaAsO2 (5 mg kg-1 ), NaAsO2 + CGA (100 mg kg-1 ), NaAsO2 + CGA (200 mg kg-1 ), or a control for 28 days. RESULTS: In the NaAsO2 -treated group, NaAsO2 induced significant renal dysfunction, oxidative damage, inflammation, and apoptosis, as demonstrated by marked increases in urea and creatinine levels accompanied by a decrease in the kidney index. Considerable increases in malondialdehyde and nitric oxide levels and parallel decreases in various antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) levels were also detected in the renal tissues of NaAsO2 -treated mice. NaAsO2 exposure was associated with marked increases in renal inflammatory markers (interleukin-1ß and tumor necrosis factor-α) and apoptosis indicators including Bax and caspase-3 levels contaminant, with a marked decrease in Bcl-2, an anti-apoptotic protein, in the NaAsO2 -treated group compared with the control group. However, pretreatment with CGA substantially mitigated the renal injury and dysfunction associated with NaAsO2 exposure by reducing tissue inflammation and apoptosis and improving the antioxidant status. The CGA pretreatment also alleviated the NaAsO2 -induced histological alterations in renal tissues. CONCLUSION: Taken together, our results suggest the efficacy of CGA in alleviating As-mediated renal tissue damage. © 2020 Society of Chemical Industry.

Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats.

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n = 7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v : v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

Luteolin protects against testicular injury induced by lead acetate by activating the Nrf2/HO-1 pathway.

Lead (Pb) is a toxic heavy metal that is harmful to humans, especially male reproductive organs. Luteolin (LUT) is a naturally occurring flavonoid with numerous biological activities. Our aim was to investigate the possible reproprotective effect of LUT against testicular deficits induced by Pb intoxication. In the present study, 28 rats were distributed into 4 groups: control, LUT (50 mg/kg), lead acetate (PbAc, 20 mg/kg), and LUT + PbAc groups, in which rats were pre-treated with LUT 3 hr before PbAc injection. All animals were treated for 7 days. Oxidative stress, inflammatory and apoptotic markers along with histopathological changes have been examined using spectrophotometric, ELISA, real-time PCR, and histopathological methods. PbAc injection elevated Pb concentration in testicular tissue and decreased levels of sex hormones. PbAc intoxication exacerbated lipoperoxidation and nitric oxide formation, depleted superoxide dismutase, and catalase activities along with glutathione and its originated enzymes (glutathione peroxidase and glutathione reductase). At the molecular level, PbAc deactivated nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in the testicular tissue. In addition, PbAc toxicity induced inflammatory and apoptotic cascades in testicular tissue as evidenced by the increased tumor necrosis factor-alpha, interleukin-1 beta, inducible nitric oxide synthase, Bax, and caspase 3, while Bcl-2 was declined. Histopathological examination of testicular tissue also revealed that PbAc caused degeneration alterations in spermatogenic cells, the spermatogenic epithelial cells were disconnected from the basement membrane, and the seminiferous tubules were vacuolated. Remarkably, pre-treatment with LUT minimized significantly the testicular damage induced by PbAc. Therefore, we conclude that LUT may have a beneficial effect against PbAc-induced testicular injury through preventing oxidative challenge, inflammation, and finally apoptosis.

Association of IL-1ß, IL-6, TNF-α, and TGFß1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome.

Recurrent spontaneous abortion (RSA) is a common pregnancy-associated complication of polycystic ovary syndrome (PCOS) which is an endocrine malfunction disease. Patients with PCOS may have several underlying contributing and interrelated factors, which have been reported in women with RSA. The incidence rate between PCOS and RSA remains uncertain. The aim of this study is to determine the possible association of IL-1ß-511C/T, IL-6-174G/C, TNF-α-1031T/C, and TGFß1-509T/C with RSA patients with or without PCOS. A total of 140 RSA patients, 70 of which were PCOS patients, and 140 healthy females with no history of RSA or PCOS were included in this study. PCR amplification, genotyping, and sequence analysis were employed to investigate the presence of the polymorphisms. The genotypic and allelic frequencies were calculated separately for each subject. Out of the four studied polymorphisms, the IL-1ß-511C/T genotype in RSA without PCOS patients (12.7%) was significantly different compared with that in control subjects (p = 0.047). For IL-6-174C/G, there was a tendency towards more CC carriers among RSA with PCOS patients (10%) than in controls (3%). The GG genotype in RSA women with PCOS (60%) was significantly different compared with that in control subjects (p = 0.033), and the GC genotype in RSA with PCOS patients (30%) showed a marginal significant difference compared with that in control subjects (p = 0.050). Significant difference was identified in the allelic frequencies in RSA patients with PCOS compared to controls (p = 0.025). IL-6-174G/C and TNF-α-1031T/C polymorphisms are significantly associated with RSA patients in Saudi patients with PCOS, while the IL-1ß-511C/T polymorphism is significantly associated with RSA patients without PCOS.

Coenzyme Q10 Activates the Antioxidant Machinery and Inhibits the Inflammatory and Apoptotic Cascades Against Lead Acetate-Induced Renal Injury in Rats.

The kidney is among the metabolic organs most susceptible to injury, particularly following exposure to xenobiotics and heavy metals. We aimed to explore the potential protective impacts of coenzyme Q10 (CoQ10) on lead acetate (PbAc)-induced nephrotoxicity in rats. Four experimental groups (n = 7) were applied as follows: control group, CoQ10 alone (10 mg/kg), PbAc alone (20 mg/kg), and PbAc with CoQ10. Exposure to PbAc led to the accumulation of Pb in the kidney and increased urea and creatinine serum levels. The deposition of Pb coupled with the elevation of malondialdehyde and nitrate/nitrite levels along with the upregulation of inducible nitric oxide synthase. Additionally, upon PbAc poisoning, glutathione content and the antioxidant enzymes were depleted along with the downregulation of Nrf2 and HO-1 expression. Moreover, PbAc injection increased the protein and mRNA levels of pro-inflammatory cytokines namely, tumor necrosis factor-alpha and interleukin-1 beta, while decreased the levels of interleukin-10, an anti-inflammatory cytokine, in the kidney. Furthermore, exposure to PbAc correlated with increased levels of pro-apoptotic markers, Bax and caspase-3, and reduced levels of the anti-apoptotic marker Bcl-2. The administration of CoQ10 alleviated the molecular, biochemical and histological changes following PbAc intoxication. Thus, CoQ10 reduces the deleterious cellular side effects of PbAc exposure due to its antioxidant, anti-inflammatory and anti-apoptotic effects.