Isaac A. Adedara

Protective effects of kolaviron and quercetin on cadmium-induced testicular damage and endocrine pathology in rats

This study evaluated the effects of kolaviron, a biflavonoid from Garcinia kola seed, and quercetin on cadmium‐induced reproductive toxicity in rats. Adult male rats were administered with either cadmium (15 mg kg−1) alone or in combination with kolaviron (200 mg kg−1) or quercetin (10 mg kg−1) daily for 5 days. Cadmium‐treated rats showed (P < 0.05) decrease in the body weight gain, testis and epididymis weights. However, upon co‐administration of kolaviron or quercetin, these changes were significantly reversed in cadmium‐treated rats. Also, administration of kolaviron or quercetin significantly prevented cadmium‐mediated decrease in sperm motility and epididymal sperm concentration and reversed the increased level of sperm abnormality to near control. In testes and sperm, cadmium treatment resulted in significant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase, whereas it increased glutathione S‐transferase activity as well as hydrogen peroxide and malondialdehyde levels. While plasma levels of triiodothyronine and tetraiodothyronine remained unaffected, the levels of testosterone, luteinising hormone and follicle stimulating hormone were decreased in cadmium‐treated rats. Cadmium treatment caused mild congestion of interstitial vessels and oedema in the testes. Taken together, kolaviron and quercetin inhibited the adverse effects of cadmium on the antioxidant enzymes, markers of oxidative stress, endocrine and testicular structure in rats.

Kolaviron, a Natural Antioxidant and Anti‐Inflammatory Phytochemical Prevents Dextran Sulphate Sodium‐Induced Colitis in Rats

The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed mainly to its antioxidant and anti‐inflammatory effects. This study investigated these effects on dextran sulphate sodium (DSS)‐induced ulcerative colitis in rats. Sulfasalazine served as standard reference in this study. Kolaviron and sulfasalazine were separately co‐administered orally at 200 mg/kg and 500 mg/kg, respectively, to dextran sulphate sodium‐exposed rats for 5 days. The result indicated that kolaviron or sulfasalazine significantly prevented DSS‐induced body weight loss as well as the incidence of diarrhoea and bleeding in DSS‐exposed rats. Kolaviron suppressed the DSS‐mediated increase in colonic nitric oxide concentration and myeloperoxidase activity and significantly prevented the increase in inflammatory mediators, interleukin‐1β and tumour necrosis factor alpha, in the colon of DSS‐treated rats. The significant depletion in colonic antioxidant status in rats exposed to DSS alone was evident by marked reduction in colonic catalase and glutathione S‐transferase activities as well as glutathione content, leading to elevated hydrogen peroxide and lipid peroxidation levels. Histopathologically, DSS alone resulted in severe epithelial erosion, total absence of goblet cells, destruction of the crypts, necrotic and distorted glands, accompanied by marked cellular mononuclear cells infiltration. However, administration of kolaviron and sulfasalazine ameliorated DSS‐induced colitis by increasing the antioxidant status decreased hydrogen peroxide and lipid peroxidation levels and attenuated the adverse effect of DSS on colon architecture. In conclusion, the anti‐colitis effect of kolaviron is related to its intrinsic anti‐inflammatory and anti‐oxidative properties.

Induction of oxidative damage in the testes and spermatozoa and hematotoxicity in rats exposed to multiple doses of ethylene glycol monoethyl ether

The effects of ethylene glycol monoethyl ether (EGEE) on the antioxidant systems of the testes and epididymal spermatozoa were investigated in rats at dose levels of 0, 100, 200 and 400 mg kg-1 body weight (bw) administered orally by gavage for 14 consecutive days. The bw gain of the EGEE-treated rats decreased significantly at 200 and 400 mg kg- 1 bw compared with the control group. There were no significant changes in the weights of the testes, epididymis, seminal vesicles and prostate glands of the EGEE-treated rats. In the testes, while EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities, it markedly increased the malondialdehyde (MDA) level, glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities at 200 and 400 mg kg-1 dose levels but vitamin C content remained unaffected in all the groups. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GST and LDH as well as in the levels of vitamin C and GSH but significantly increased the MDA level and SOD activity compared with the control rats. Histopathological examination showed severe degeneration of the testes, such as generalized erosion and necrosis of the germinal epithelium of the testes, but mildly affected the epididymis at 400 mg kg-1 dose only. Data on spermatozoa analysis of EGEE-treated rats revealed significant decrease in the epididymal spermatozoa number, testicular spermatozoa number, daily spermatozoa production and spermatozoa motility but significantly increased the total spermatozoa abnormalities without affecting the spermatozoa live-dead ratio at all dose levels when compared with the control group. Results of haematological examination showed that white blood cells (WBC), platelets neutrophils and mean corpuscular haemoglobin concentration (MCHC) were significantly lower whereas lymphocytes were increased in 200 and 400 mg/kg EGEE-exposed rats than in the controls. EGEE at 100 mg/kg bw produced minor effect on haematological parameters but adversely affected testes and spermatozoa. In summary, short term administration of EGEE is hematotoxic and gonadotoxic and its effects on male reproduction could be due to the induction of oxidative stress in testes and spermatozoa.

Aflatoxin B1 and ethanol co-exposure induces hepatic oxidative damage in mice

The present study investigated the effects of aflatoxin B1 (AFB1) and ethanol co-exposure on biomarkers of hepatic damage in mice. Four groups of adult male mice were treated for 7 consecutive days. Control mice received corn oil alone at a dose of 2 mL/kg bw. One group was treated with ethanol at a dose of 500 µL/kg bw and another group administered 9 mg/kg bw of AFB1 dissolved in corn oil. The fourth group was co-administered with ethanol and AFB 1. The body and liver weights of treated mice decreased significantly when compared with corresponding control. Alone, ethanol and AFB1 treatment separately increased serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP). Alcohol dehydrogenase (ALD) activity was markedly elevated in ethanol-treated mice but was unaffected by AFB1 treatment. Co-exposure of AFB1 and ethanol escalated the activities of these serum enzymes. Administration of ethanol and AFB1 separately resulted in significant decrease in both non-enzymatic antioxidant glutathione (GSH) level and enzymatic antioxidant catalase (CAT) and glutathione-S-transferase (GST) activities, whereas lipid peroxidation was markedly elevated. Superoxide dismutase activity and vitamin C level remained unaffected in all treatment groups. Co-exposure of animals to ethanol and AFB1 showed additive effects on the activities of GST and CAT as well as on the GSH level. Histopathological study revealed that these compounds interact together to exacerbate their individual effects on the liver. In summary, the data presented showed that AFB1 and ethanol co-exposure induced severe oxidative damage to the liver of mice and as such humans consuming excessive amount of ethanol and diets contaminated with AFB1 simultaneously may be at greater risk of the hepatotoxic effects of these compounds.

Chemoprotection of ethylene glycol monoethyl ether-induced reproductive toxicity in male rats by kolaviron, isolated biflavonoid from Garcinia kola seed

The present study investigated the protective effect of kolaviron, a biflavonoid from the seed of Garcinia kola, on ethylene glycol monoethyl ether (EGEE)–induced reproductive toxicity in male rats. The protective effect of kolaviron was validated using vitamin E, a standard antioxidant. EGEE was administered at a dose of 200 mg/kg. Other groups of rats were simultaneously treated with kolaviron (100 and 200 mg/kg) and vitamin E (50 mg/kg) for 14 days. EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities but markedly increased the glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities in the testes. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GPx, GST and LDH as well as in the level of GSH but significantly increased SOD activity with concomitant increase in hydrogen peroxide and malondialdehyde levels in both testes and spermatozoa. EGEE-exposed rats showed marked testicular degeneration with concomitant decrease in spermatozoa quantity and quality. Overall, EGEE causes reproductive dysfunction in rats by altering antioxidant systems in the testes and spermatozoa. Kolaviron or vitamin E exhibited protective effects against EGEE-induced male reproductive toxicity by enhancement of antioxidant status and improvement in spermatozoa quantity and quality.

Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats

The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200mg/kg) singly or in combination with kolaviron (100 and 200mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.

Pharmacological Activity of 6‐Gingerol in Dextran Sulphate Sodium‐induced Ulcerative Colitis in BALB/c Mice

Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6‐gingerol in a mouse model of dextran sulphate sodium (DSS)‐induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co‐treated with 6‐gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment‐related effects of 6‐gingerol in DSS‐treated mice. Administration of 6‐gingerol significantly reversed the DSS‐mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6‐gingerol significantly suppressed the circulating concentrations of interleukin‐1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS‐treated mice. 6‐Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS‐treated mice. 6‐Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate. Copyright

Induction of oxidative stress in liver and kidney of rats exposed to Nigerian bonny light crude oil.

The local population of Niger‐Delta in the Southern part of Nigeria have used bonny light crude oil (BLCO) as a remedy for various ailments and are exposed to some extent to this widespread environmental contaminant or its metabolites through the food chain. BLCOs hepatorenal toxicity was studied using oxidative stress indices to elucidate the precise nature and mechanism of action. BLCO was orally administered at concentrations of 0, 200, 400, and 800 mg kg−1 to adult male rats for 7 days. After exposure, kidney weight was unaffected, but liver weight decreased significantly at 800 mg kg−1 only compared with control. BLCO exposure resulted in dose‐dependent elevation of serum aminotransferases, total bilirubin, urea, and creatinine. Activities of superoxide dismutase and catalase decreased significantly, whereas γ‐glutamyltransferase activity and the level of glutathione increased significantly in BLCO‐treated animals compared with control in both liver and kidney of rat. Renal activities of glucose‐6‐phosphatase and 5′‐nucleotidase markedly decreased in a dose‐dependent manner in BLCO‐exposed rats. In addition, the levels of hydrogen peroxide and lipid peroxidation significantly increased, dose dependently, in liver and kidney of BLCO‐treated rats compared with control. BLCO‐treated rats showed marked degeneration of kidney evident in cortical hemorrhages, tubular necrosis, protein casts, and cellular infiltration. However, no treatment‐related liver histopathology was observed. The results suggested that BLCO elicits disruption of antioxidant status and concomitant elevation of hydrogen peroxide and lipid peroxidation differentially in liver and kidney of rats. The hepatorenal toxicity of BLCO could be due to induction of oxidative stress in liver and kidney.

Hepatic, testicular and spermatozoa antioxidant status in rats chronically treated with Garcinia kolaseed.

ETHNOPHARMACOLOGICAL RELEVANCE Garcinia kola seed is commonly used in African Traditional Medicine as a remedy for liver disorders, hepatitis, bronchitis, throat infections as well as an aphrodisiac and fertility enhancing substance. Owing to the abundance of complex mixture of phenolic compounds in Garcinia kola seed, there is a growing safety concern on its long-term use in folklore medicine. The present study evaluated the hepatic, testicular and spermatozoa antioxidant status in rats chronically treated with Garcinia kolaseed. MATERIALS AND METHODS Adult male Wistar rats were randomly assigned to four groups of 10 rats each and were orally administered with Garcinia kola at 0, 250, 500 and 1000mg/kg for 6consecutive weeks. Clinical observations, serum biochemistry, oxidative stress biomarkers, spermatozoa parameters and histopathological examination of the organs were assessed to monitor treatment-related adverse effects inrats. RESULTS Long-term treatment of Garcinia kola had no adverse effect on the spermatozoa characteristics but significantly elevated testosterone concentration when compared to the control group. Improvement of antioxidant systems was accompanied by a significant decrease in malondialdehyde level in the liver, testes and spermatozoa of Garcinia kola-treated rats. Histological observation revealed that chronic administration of Garcinia kola had no effect on the liver and testes at all doses when compared with control. CONCLUSION Garcinia kola seed boosts the antioxidant status and exhibits no adverse effect on the liver, testes and spermatozoa after a long-term oral exposure inrats.

Municipal landfill leachate induces hepatotoxicity and oxidative stress in rats.

Human beings are more often exposed to complex mixtures of hazardous chemicals than single toxicant. The present study investigated the effects of Olushosun municipal landfill leachate (OMLL) from Ojota in Lagos State of Nigeria on hepatic function and some biomarkers of oxidative stress in adult rats. Physicochemical characteristic analysis of OMLL showed that while total alkalinity, total acidity, total hardness, biochemical oxygen demand and chemical oxygen demand were 3-fold, 2-fold, 4-fold and 1-fold, respectively, concentrations of heavy metals analysis showed that copper, lead, cadmium, arsenic, cobalt, chromium and mercury were 9-fold, 4-fold, 21-fold, 1320-fold, 7-fold, 5-fold and 4-fold, respectively, higher than acceptable limits by regulatory authorities. The OMLL was administered at 0, 10, 20, 30 and 40% concentrations to adult male rats for 14 days. Following exposure, serum was collected for serum biochemistry assays and liver was collected to determine the antioxidant status. Exposure of animals to 10, 20, 30 and 40% OMLL resulted in 3%, 31%, 52% and 83% increase in aspartate aminotransferase activity, whereas it elevated alanine aminotransferase activity by 10%, 25%, 30% and 49%, respectively, when compared with the control. While OMLL administration significantly increased catalase activity, a sequential decrease in reduced glutathione level and in superoxide dismutase and glutathione-S-transferase activities with concomitant increase in malondialdehyde level were observed, when compared with the control. Collectively, the hepatotoxicity of OMLL could be due to the induction of oxidative stress and may suggest possible health hazards in subjects with occupational or environmental exposure.