Possible mechanisms involved in the protective effect of lutein against cyclosporine-induced testicular damage in rats.

Oxidative stress and aberrant inflammatory response have important implications in cyclosporin-induced reproductive functions. Previous studies have shown that agents with antioxidant and anti-inflammatory activities might be beneficial in reversing cyclosporin-induced reproductive impairment. Lutein is a naturally occurring compound with antioxidant and anti-inflammatory properties. However, the effect of lutein against cyclosporin-induced reproductive impairment remains in complete. Hence, we investigated the protective effect of lutein, specifically focusing on the role of nuclear factor erythroid 2 related factor-2 (Nrf2)/heme-oxygenase-1 (HO-1)/connexin-43 (Cx-43) upregulation system against cyclosporine-induced reproductive impairment. Six male Wistar rats were allotted into 5 groups and given daily gavage of cyclosporine (40 mg/kg) and/or lutein (30 mg/kg) for four (4) weeks or in combination, respectively. The testicular antioxidant scaffolds: superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), add to sulfhydryl (T-SH), non-protein sulfhydryl (NP-SH), glutathione reductase (GR), glutathione-S -transferase (GST), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), myeloperoxidase (MPO), testicular proinflammatory cytokines, apoptotic related protein, nucleic acids, sialic acid, testicular proton pump ATPase, stress responsive protein, BTB-related protein and total protein levels in the testes were assayed thereafter. Cyclosporin significantly increased NOX-1, TNF-α, IL-1ß, MPO, caspase-3 and -9 levels, which were reversed by lutein. Lutein reversed cyclosporin-induced decreases in Nrf2, HO-1, BCL-2, cytochrome C, with corresponding increase in CAT, SOD, GSH, T-SH, NP-SH, GST, GR, GSH-Px, and Cx-43 levels compared to cyclosporin groups. Lutein also abates cyclosporin-induced alterations Na + -K + -ATPase activities. Our findings showed that lutein's protective effect against cyclosporin-induced reproductive impairment might be associated with mechanisms linked to its antioxidant, anti-apoptotic, and anti-inflammatory properties, notably through up-regulation of Nrf2/HO-1/Cx-43 signaling and down-regulation of NOX-1 signaling.

Ginkgo biloba modulates ET-I/NO signalling in Lead Acetate induced rat model of endothelial dysfunction: Involvement of oxido-inflammatory mediators.

This study investigated the modulatory effect of Ginkgo biloba extract on lead acetate-induced endothelial dysfunction. Animals were administered GBE (50 mg/kg and 100 mg/kg orally) after exposures to lead acetate (25 mg/kg orally) for 14 days. Aorta was harvested after euthanasia, the tissue was homogenised, and supernatants were decanted after centrifuging. Oxidative, nitrergic, inflammatory, and anti-apoptotic markers were assayed using standard biochemical procedure, ELISA, and immunohistochemistry, respectively. GBE reduced lead-induced oxidative stress by increasing SOD, GSH, and CAT as well as reducing MDA levels in endothelium. Pro-inflammatory cytokines (TNF-α and IL-6) were reduced while increasing Bcl-2 protein expression. GBE lowered endothelin-I and raised nitrite levels. Histological changes caused by lead acetate were normalised by GBE. Our findings suggest that Ginkgo biloba extract restored endothelin-I and nitric oxide functions by increasing Bcl-2 protein expression and reducing oxido-inflammatory stress in endothelium.

Ginkgo biloba supplement abates lead-induced endothelial and testicular dysfunction in Wistar rats via up-regulation of Bcl-2 protein expression, pituitary-testicular hormones and down-regulation of oxido-inflammatory reactions.

BACKGROUND: Apoptotic and oxido-inflammatory pathways have been found to be up-regulated in lead acetate poisoning which has been associated to endothelial and testicular dysfunctions. It is yet uncertain, nevertheless, if treatment with Ginkgo biloba supplements (GBS), a flavonoid-rich natural product can lessen the adverse effects of lead on endothelial and testicular functions. This study investigated the impact of Ginkgo biloba supplementation on lead-induced endothelial and testicular dysfunctions. METHODS: The animals were treated with GBS (50 mg/kg and 100 mg/kg orally) for 14 days following oral exposure to lead acetate (25 mg/kg) for 14 days. After euthanasia, blood samples, epididymal sperm, testes, and aorta were collected. The quantities of the hormones (testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH), as well as the anti-apoptotic, oxidative, nitrergic, inflammatory markers, were then determined using immunohistochemistry, ELISA, and conventional biochemical methods. RESULTS: GBS reduced lead-induced oxidative stress by increasing the levels of the antioxidant enzymes catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD), while lowering malondialdehyde (MDA) in endothelium and testicular cells. Normal testicular weight was restored by GBS which also decreased endothelial endothelin-I and increased nitrite levels. TNF-α and IL-6 were decreased while Bcl-2 protein expression was enhanced. Lead-induced alterations in reproductive hormones (FSH, LH, and testosterone) were also restored to normal. CONCLUSION: According to our result, using Ginkgo biloba supplement prevented lead from causing endothelial and testicular dysfunction by raising pituitary-testicular hormone levels, boosting Bcl-2 protein expression and lowering oxidative and inflammatory stress in the endothelium and testes.

Terminalia catappa attenuates phenylhydrazine-induced anaemia and hepato-renal toxicity in male Wistar rat by boosting blood cells, modulation of lipoproteins and up-regulation of in vivo antioxidant armouries.

AIM: This study investigated the haematinic, antihyperlipidaemic, hepato-renal protective effects of Terminalia catappa aqueous leaf extract on male Wistar rats exposed to phenylhydrazine toxicity. METHODS: Animals were exposed to phenylhydrazine (PHZ) 50 mg/kg intraperitoneal for two consecutive days thereafter, treated with T. catappa extract (100 mg/kg and 200 mg/kg) orally for 21 days. After the experimentation, animals were sedated with ketamine (70 mg/kg) and euthanized by cervical dislodgement. Blood and organs were collected for haematology and biochemical studies following standard laboratory methods. RESULTS: Our study showed that T. catappa significantly increased erythrocytes, haemoglobin, haematocrit and high density lipoprotein as well as down-regulating leukocytes, thrombocytes, ALP AST, ALT creatinine, urea, total cholesterol as well as low density lipoprotein. The liver, kidney and spleen antioxidant defence were also up-regulated against the adverse effect caused by phenylhydrazine exposure. CONCLUSION: Terminalia catappa attenuated Phenylhydrazine-induced anaemia and hepato-renal toxicity in male Wistar rat by boosting blood cells, modulation of lipoproteins and up-regulation of in vivo antioxidant armouries.

Cabbage juice supplementation abrogates Lead acetate-induced haematological and haemorheological imbalances in male Wistar rat.

Lead is a hazardous naturally found heavy metal that has been reported to induce haematological alterations. Whether cabbage, a commonly consumed vegetable rich in antioxidants and anticancer compounds, can mitigate these alterations remains unknown. This study investigated the protective effect of cabbage juice against Lead-induced haematological changes. Twenty (20) male Wistar rats were randomly selected into four groups (n = 5) and given distilled water (1 ml/100 g b.wt), Lead acetate (25 mg/kg b.wt), Cabbage juice (1 ml/100 g b.wt), and Lead acetate with Cabbage juice. All treatments were given orally for 28 days. Lead exposure induces normocytic normochromic anemia with substantial leukocytosis, lymphocytopenia, and hyperfibrinogenemia. Lead-intoxicated animals had significantly higher haemolysis and prolonged clotting times. However, cabbage juice reverses these adverse haematological and haemorheological changes induced by Lead acetate. Conclusively, cabbage juice demonstrated antioxidant, anti-inflammatory, anti-thrombotic, and immunomodulatory properties, as well as the ability to protect the red blood cell membrane from damage caused by Lead-induced osmotic stress.

Dietary Supplementation with D-Ribose-L-Cysteine Prevents Hepatic Stress and Pro-Inflammatory Responses in Male Wistar Rats Fed a High-Fructose High-Fat Diet.

Diets rich in fats and fructose are associated with the pathogenesis of oxidative stress-induced non-alcoholic fatty liver disease. Therefore, we investigated the effect of D-ribose-L-cysteine (DRLC) in high-fructose high-fat (HFHF) diet-fed rats. Twenty rats (n = 5), divided into four groups, were simultaneously exposed to HFHF and/or DRLC (250 mg/kg) orally during the 8 weeks of the study. Results showed that HFHF precipitated pro-inflammation and selective disruption of the oxidative stress markers. There were significant decreases in the level of antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), hepatic SOD and GPX. Significant increases in serum levels of uric acid (UA), tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and hepatic Xanthine oxidase (XO) were observed in the HFHF compared to the control. In the HFHF + DRLC group, oxidative stress was mitigated due to differences in serum levels of SOD, GPX, TAC, TNF-α, liver SOD, and XO relative to control. The administration of DRLC alone caused significant reductions in malondialdehyde, UA and CRP and a significant increase in SOD compared to the control. DRLC prevents hepatic and systemic oxidative stress and pro-inflammatory events in HFHF diet-fed rats.

Up-regulation of B-cell lymphoma factor-2 expression, inhibition of oxidative stress and down-regulation of pro-inflammatory cytokines are involved in the protective effect of cabbage (Brassica oleracea) juice in lead-induced endothelial dysfunction in rats.

BACKGROUND: Oxido-inflammatory stress and dysregulation of nitric oxide (NO) system has been implicated in lead toxicity. Cabbage is an antioxidant-rich household vegetable with plethora of therapeutic potentials. The present study investigated the anti-oxido-inflammatory activity of cabbage in lead-induced endothelial dysfunction. METHODS: Twenty (20) male Wistar rats were selected into four groups (n = 5) and treated with distilled water (1 mL/100 g b.wt), lead acetate (25 mg/kg b.wt), cabbage juice (1 mL/100 g b.wt) and lead acetate (25 mg/kg b.wt) plus cabbage juice (1 mL/100 g b.wt) respectively. Treatment was done orally for 28 days, thereafter, oxidative stress (SOD, CAT, GSH, and MDA), inflammatory (TNF-α and IL-6) and apoptotic (Bcl-2) markers were assayed using standard biochemical assays as well as histoarchitectural study of the endothelium. RESULTS: The results showed that they were significant increase in MDA, ET-1, TNF-α and IL-6 while SOD, GSH, CAT, NO and Bcl-2 protein expression were decreased in Lead exposed animals. Endothelial histoarchitecture was also altered. Following Cabbage juice treatment, MDA, ET-I, TNF-α and IL-6 were down-regulated while SOD, GSH, CAT, NO and Bcl-2 protein expression were up-regulated. Histoarchitecture was significantly recovered. CONCLUSION: The study suggests that cabbage juice could mitigates Lead-induced endothelial dysfunction by modulating oxido-inflammatory and anti-apoptotic mediators. DATA AVAILABILITY: All data are available upon request.

Cabbage (Brassica oleracea) mitigates lead (II) acetate-induced testicular dysfunction in Wistar rats via up-regulation of Bcl-2 protein expression, pituitary-testicular hormonal axis and down-regulation of oxido-inflammatory reactions.

Oxido-inflammatory stress has been involved in lead-induced testicular dysfunction and plants rich in anti-oxidants has been reported to be beneficial in combating heavy metal poisonings in animal studies. However, cabbage juice protective effect on lead-induced testicular dysfunction was investigated in this study. Twenty male Wistar rats were selected into four (n = 5) groups and given distilled water (1 ml/100 g body weight), lead acetate (25 mg/kg body weight), cabbage juice (1 ml/100 g body weight), and lead acetate with cabbage juice, respectively. All treatments were administered orally for 28 days. Sperm count, motility, viability, testosterone, luteinising hormone and follicle-stimulating hormone, testicular Bcl-2 expression, and enzymatic anti-oxidant capabilities were considerably (p < 0.05) decrease in lead-treated animals. However, cabbage juice significantly (p < 0.05) elevated these parameters. Testicular malondialdehyde, tumour necrosis factor-α, nitric oxide and interleukin-6 was elevated by lead acetate. When comparing cabbage juice-treated animals to lead-treated animals, all of these parameters were considerably (p < 0.05) downregulated in cabbage juice-treated animals. Following lead administration, the testes' histomorphological alterations were not totally recovered despite therapy with cabbage juice. Conclusively, this study suggest that cabbage juice mitigates testicular dysfunction associated with lead exposure via its anti-oxidant, anti-inflammatory, anti-apoptotic and androgenic properties.

Cabbage juice protect against lead-induced liver and kidney damage in male Wistar rat.

AIM: Liver and kidney has been implicated in Lead toxicity and this has been linked to oxidative damage. On the other hand, cabbage is one of the widely consumed vegetables with a plethora of health benefits. This present study investigated the protective effect of cabbage juice on lead-induced toxicity in male Wistar rats. METHODS: Twenty male Wistar rats were randomly divided into four groups (n = 5) and were treated with distilled water (1 ml/100 g b.wt), Lead acetate (25 mg/kg b.wt), cabbage juice (1 ml/100 g b.wt) and Lead acetate plus cabbage juice respectively. All treatments were administered orally for 28 days. Following euthanasia, blood was collected and serum decanted for biochemical assay and liver and kidney tissues were harvested, prepared for antioxidant activity and histological study. RESULT: Cabbage juice significantly attenuated Lead-induced liver and kidney dysfunction by lowering serum concentrations of urea, creatinine, ALP, AST and ALT. Antioxidants (SOD, CAT, GSH) were also upregulated in liver and kidney tissues. Cabbage juice restored the histoarchitectural changes caused by lead intoxication. CONCLUSION: Cabbage juice consumption protected the liver and kidney against lead-induced toxicity by enhancing in vivo anti-oxidant defense system.

Ginkgo biloba Supplement Reverses Lead (II) Acetate-Induced Haematological Imbalances, Hepatic and Renal Dysfunctions in Male Wistar Rat.

Lead is a heavy metal abundant in nature that causes haematological imbalances, and hepatic and renal dysfunction, and this imbalance has been linked to oxidative stress. Several reports have shown that natural products are implicated in ameliorating metal poisonings. Ginkgo biloba is a flavonoid-rich natural herbal supplement with several pharmacological properties. The present study investigated effect of Ginkgo biloba supplement (GBS) on lead-induced toxicity. Animals were given a lead dose of 25 mg/kg for 14 days orally and then given Ginkgo biloba supplements of 50 mg/kg and 100 mg/kg orally for 14 days. Animals given GBS had significantly improved haematological and rheological parameters. GBS showed a protective impact in terms of improved kidney and liver histology, anti-oxidant enzyme activity (CAT, SOD, GSH, and MDA), organ function indices, and a lower rate of erythrocyte osmotic fragility. Conclusively, Ginkgo biloba supplementation attenuated lead toxicity by normalization of haematological imbalances, and hepatic and renal dysfunction as well as maintaining erythrocyte membrane integrity.

Maternal hypothyroidism prolongs gestation period and impairs glucose tolerance in offspring of Wistar rats.

OBJECTIVES: Pregnancy is a critical period keenly regulated by both maternal and foetal factors and a shift in these factors could result in severe complications manifesting in foetal and adult life. However, maternal hypothyroidism before and/or during pregnancy is a critical factor. This study investigated the effect of maternal hypothyroidism on glucose tolerance and thyroid function in male and female offspring. METHODS: Fifteen adult female Wistar rats were divided into three groups: Group 1 (sham-control), Group 2 (thyrodectomized) and Group 3 (thyroidectomised + L-thyroxine treated). Blood thyroxine (T4) level was measured on the day 10 after thyroidectomy in Groups 1 and 2, and day 35 in Group 3. Males were introduced to the female rats after T4 measurement. At PND-112, T4 levels of their offspring were measured. Oral Glucose Tolerance Test (OGTT) was measured in offspring at PND-133. RESULTS: Thyroxine reduced significantly in Group 2 and their offspring (male and female) compared to Group 3 while gestation period was prolonged significantly in Group 2 compared to Group 1. Hypothyroid male offspring showed depressed glucose tolerance, however, no effect was observed in female offspring. CONCLUSIONS: This study suggests that maternal hypothyroidism prolonged gestation period, induced foetal hypothyroidism in both genders and depressed glucose tolerance in male offspring.

Co-administration of prazosin and propranolol with glibenclamide improves anti-oxidant defense system in endothelial tissue of streptozotocin-induced diabetic Wistar rats.

Background Due to increasing prevalence of diabetes and associated endothelial dysfunction, this study was carried out to investigate the effects of co-administration of adrenoceptor blockers (prazosin and propranolol) and glibenclamide on plasma biomarkers of endothelial functions in diabetic rats. Methods Experiments were carried out on 35 male Wistar rats (170-200 g). They were divided into seven groups (n=5) as follows: normal control, diabetic control, diabetic + glibenclamide (GLB-5mg/kg/day), diabetic+ prazosin (PRZ-0.5 mg/kg/day), diabetic + PRZ + GLB, diabetic + propranolol (PRP-10 mg/kg/day), diabetes + PRP + GLB. Experimental diabetes was induced with streptozotocin (60 mg/kg) and drugs were administered orally for 3 weeks. Blood pressure was measured and animals were sacrificed afterwards. Blood samples were collected by cardiac puncture, and major marker of endothelial functions, nitric oxide derivatives (NOx), as well as superoxide dismutase (SOD) and malondialdehyde (MDA) were measured on the plasma. The aorta was harvested for histological examination. Data were subjected to descriptive statistics and analysed using ANOVA at α 0.05. Results There was a significant increase in levels of NOx and SOD, and a decrease in MDA level in diabetic treated groups compared to diabetic control. Mean blood pressure increased in diabetic control and diabetic + GLB group when compared with normal control, while it was mildly reduced in diabetic group treated with PRZ and PRP, and co-administered GLB. More so, Aorta histology was altered in diabetic control groups when compared with normal control and all diabetic treated groups. Conclusions Results from this study suggest that PRZ, PRP, and GLB (singly and in combined therapy) could have a restorative effect on endothelial functions in diabetes.