Downregulation of redox imbalance and iNOS/NF-ĸB/caspase-3 signalling with zinc supplementation prevents urotoxicity of cyclophosphamide-induced hemorrhagic cystitis in rats.

AIM: Cyclophosphamide (CYP) chemotherapy induces bladder toxicity and hemorrhagic cystitis in cancer patients constituting a current clinical concern. Oxidative inflammatory cascades have been implicated as the mechanism contributing to CYP bladder urotoxicity. We thus assayed to explore whether zinc (Zn) supplementation could mitigate CYP-induced urotoxicity and evaluate the possible underlying mechanism in rats. MAIN METHOD: Rats were orally administered Zn (100 mg/kg b.w./day) for 10 days against urotoxicity induced by single injection of CYP (150 mg/kg b.w., ip) on day 7. KEY FINDINGS: CYP significantly depressed bladder activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels, whereas malondialdehyde level was increased prominently. In addition, CYP induced marked increases in the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by histological alterations. CYP prominently increased bladder inducible nitric oxide synthase (iNOS) activity, nuclear factor-kappa B (NF-ĸB) and expression of caspase-3 protein. Zinc supplementation considerably abrogated the bladder urotoxicity by restoring redox balance, proinflammatory and apoptotic cascades and alleviated histopathological changes. SIGNIFICANCE: This is the first to reveal zinc potential to prevent CYP-induced urotoxic hemorrhagic cystitis via restoring redox balance and enhancing anti-inflammatory and antiapoptotic mechanisms in rat bladder.

Aqueous peel extract of Citrus aurantifolia attenuated tramadol-mediated testicular oxidative stress, apoptosis, inflammations and histo-architectural degeneration in a rat model

Tramadol is one of the most commonly abused drugs. It has been reported to impair testicular function in models. Citrus aurantifolia is a citrus fruit used extensively in beverages and herbal preparations. This study investigated the modulating role of aqueous zest extract of Citrus aurantifolia (AZECA) against tramadol-mediated testicular toxicity in rat. Twenty-five male rats were assigned to 5 groups and orally treated with distilled water (negative control) for 28 days, 30 mg/kg of tramadol (positive control) for 14 days, 30 mg/kg of tramadol for first two weeks and 50 (treatment 1) and 100 mg/kg (treatment 1) of AZECA for the last 2 weeks. Biochemical markers were evaluated and testes were stained routinely for morphometry. Results shows a significant (p<0.05) decrease in testosterone, FSH and LH, SOD, CAT and a significant increase MDA, IL-1 and TNF-alpha evidenced by a significant (p < 0.05) reduction in volumetric proportion of interstitium and seminiferous tubules-tunica propria, macrophages, blood vessels and lymphatic space, macrophages, connective tissue, diameter, cross-sectional area and number of pro-files of seminiferous tubules per unit area in group treated with tramadolalone. These parameters were significantly (p<0.05) negated in groups that had AZECA supplementation. This study has demonstrated that treatment with AZECA exerted a potent testiculo-protective activity against tramadol-induced testicular injury in rats

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Nephroprotective activity of virgin coconut oil on diclofenac-induced oxidative nephrotoxicity is associated with antioxidant and anti-inflammatory effects in rats.

OBJECTIVE: Diclofenac is a non-steroidal anti-inflammatory drug linked with considerable organ toxicity caused via increased generation of reactive oxygen species. We evaluated whether the antioxidant effect of virgin coconut oil (VCO) could prevent diclofenac-induced oxidative nephrotoxicity in rats. MATERIALS AND METHODS: Randomized rats were pre-supplemented orally with VCO (5 or 10 ml/kg body weight) from day 1 to 24, and injected with normal saline or diclofenac (100 mg/kg) from day 22 to day 24 intraperitoneally. RESULTS: Diclofenac significantly (p<0.05) increased serum urea and creatinine levels. Renal tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels markedly (p<0.05) increased, whereas renal glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activities considerably (p<0.05) decreased compared to normal control. Histopathological alterations were caused by diclofenac. However, treatment with oral VCO for 21 days prior to diclofenac administration, attenuated histological renal damage, and restored antioxidant enzyme activities and TNF-α levels in kidney. CONCLUSION: These findings revealed that VCO has potential benefits to prevent diclofenac-induced nephrotoxic damage.

Modulation of the Lipid Profile, Hepatic and Renal Antioxidant Activities, and Markers of Hepatic and Renal Dysfunctions in Alloxan-Induced Diabetic Rats by Virgin Coconut Oil.

BACKGROUND: Research studies that holistically investigated the effect of administration of Virgin Coconut Oil (VCO) on diabetic humans or animals are limited in literature. OBJECTIVE: To investigate the effect of administration of VCO on lipid profile, markers of hepatic and renal dysfunction, and hepatic and renal antioxidant activities of alloxan induced diabetic rats. METHODS: Twenty-four male albino rats were used, and they were divided into four groups of six rats each. Group 1 (Normal Control, NC) received distilled water (1 mL/kg); Group 2 (VCO Control) received VCO (5 mL/kg); Group 3 (Diabetic Control, DC) received distilled water (1 mL/kg); Group 4 (Test Group, TG) received 5 ml/kg of VCO. RESULTS: There were no significant differences in blood glucose, body weights, relative liver weights, relative kidney weights, hepatic and renal Superoxide Dismutase (SOD) activities, Malondialdehyde (MDA), albumin, aspartate Amino Transaminase (AST), alanine Amino Transaminase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, uric acid, total cholesterol, triacylglycerol, Very Low Density Lipoprotein cholesterol (VLDL) and Low Density Lipoprotein cholesterol (LDL) concentrations; significant increases in renal Glutathione (GSH), hepatic catalase, Glutathione Peroxidase (GPx) and GSH but significant reduction in renal GPx and catalase activities of VCO control group compared with NC group. There were significant increases in blood glucose, relative liver and kidney weights, hepatic GPx, hepatic and renal MDA concentration, ALP, AST, ALT, urea, creatinine, uric acid, triacylglycerol, total cholesterol, LDL and VLDL concentrations; and significant decreases in body weight, hepatic SOD and GSH activities and albumin concentration but no significant difference in hepatic catalase activity of DC group compared with NC group. Administration of VCO to diabetic rats positively modulated these parameters compared with the diabetic control. CONCLUSION: The study showed the potentials of VCO in the management of hyperlipidemia, renal and hepatic dysfunctions imposed by hyperglycemia and by oxidative stress in diabetic rats.

Histochemical and morphometric evidences of the curative role of aqueous zest extract of Citrus sinensis on anti-neoplastic drug-induced testicular degeneration in animal models

This study examined the curative effects of aqueous zest extract of Citrus sinensis and Cisplatin (CIS)-induced testicular degeneration. Sixteen male Wistar rats (10 to 12 weeks old) weighing 306-238 g were used in this study. The animals were divided as follows: Group A was treated orally with 2.5 ml/kg body weight/daily; Group B was treated with a single dose of 10 mg/kg body weight; Group C and D rats were given a single dose of 10 mg/kg body weight of cisplatin and then treated orally with 10 and 40 mg/kg body weight of aqueous zest extract of Citrus sinensis. The procedure lasted for 8 weeks.Results showed a significant (p< 0.05) decrease in final body weight, testis weight, testis weight/body weight ratio, normal sperm morphology (p<0.01) and a significant decrease in tubular diameter (p > 0.01), perimeter (p > 0.01 and) and length (p > 0.001), width (p >0.05) and increase (p > 0.05), germinal epithelia height, cross-sectional area, number of profiles per unit area and numerical density of seminiferous tubules. Rats that were treated with CIS alone without pre-treatment or post-treatment with extract showed marked degeneration and atrophied seminiferous tubules with absence of late stage germ cells. There was also a reduction in PAS-positive materials of the rats treated with Cisplatin. These parameters were however ameliorated in the groups that were post-treated with the aqueous zest extract of Citrus sinensis. This could have been as a result of its antioxidant and free radical scavenging potentials

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Protective and curative role of Citrus sinensis peel on cadmium-induced testicular and spermatic damage: a morphometric and immunohistochemical evaluation using monoclonal antibodies against Ki-67 and proliferating cell nuclear antigen

This study examined the protective and curative effects of aqueous zest extract of Citrus sinensis on Cadmium-induced testicular tumor in animal models. Twenty four male Wistar rats (10 to 12 weeks old) weighing 165-275 g were divided into group A (treated orally with 2.5 ml/kg body weight/daily of normal saline), Group B (treated intraperitoneally with a single dose of 5mg/kg of cadmium), group C (Treated intraperitoneally with 5 mg/kg of cadmium before 10 mg/kg aqueous zest extract of Citrus sinensis orally), group D (treated with 5mg/kg of cadmium before 40 mg/kg extract), group E (treated with 10 mg/kg extract before 5 mg/kg of cadmium) and group F (treated with 40 mg/kg extract before 5mg/kg of cadmium). The procedure lasted for 8 weeks. Group B rats showed a significant (p< 0.05) decrease in testis weight, testis volume, sperm count (p > 0.001), sperm motility (p > 0.001), abnormal sperm morphology (p<0.001) and a significant decrease in tubular diameter, length (p <0.05), cross sectional area, width, germinal epithelia height, numerical density (p <0.01), perimeter, number (p < 0.001) and a significant increase in tubular lumen of the seminiferous tubules. Rats that were treated with cadmium without pre-treatment or post-treatment with extract showed marked degeneration and atrophied seminiferous tubules with absence of late stage germ cells. There was also a reduction in proliferative cell nuclear antigen (PCNA) materials and Ki67 positive cells in these rats. Interestingly, all these parameters were however attenuated in the groups that were pre-treated and post-treated with the extract. Taken together therefore, it was concluded that aqueous zest extract of Citrus sinensis have protective and curative roles in the abatement of cadmium-induced testicular tumor and that these effects might be as a result of the antioxidant and free radical scavenging potentials of these neutraceuticals

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Pathophysiology of varicocele: evidence for oxidative stress as a mechanism pathway

There has never been an unswerving animal model for the study of varicocele; neither has a stable result been obtained. This has been as a result of personal interpretation of venous anatomical differences between human and rat models. Although the pathogenesis of varicocele remains uncertain, there is a growing body of data implicating hyperthermia, venous pressure, testicular blood flow, hormonal imbalance, toxic substances, and reactive oxygen species.The present study established the role of oxidative stress in the pathogenesis of varicocele using animal models. Four groups of rats were used, the first group served as the control, while the second, third and fourth groups of rats were varicocelized. The third and fourth group, in addition, had intraperitoneal and intramuscular treatment of 20 mg/kg and 25 mg/kg body weight of zinc chloride and alpha-tocopherol respectively. Fifty six days after, testicular weights and volumes, histology, morphometry, enzymatic and non-enzymatic antioxidants were evaluated.Result showed that the testes of varicocelized models treated with antioxidants had better oxidative status, geometric values and histological profiles compared to the untreated varicocelized models. These results indicated and validated the role of reactive oxygen in the pathogenesis of varicocele (AU)

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