Endocrine disruption and oxidative stress implications of artemether-lumefantrine combination therapy in the ovary and uterus of rats.

In the current study, we evaluated the endocrine disruption effect and oxidative stress implication of therapeutic dose of artemether-lumefantrine combination therapy on the ovary and uterus of rats. In this respect, female rats were divided into four groups: animals were per orally treated with tween 80 (control), artemether (4 mg kg-1 body weight), lumefantrine (24 mg kg-1 body weight) and artemether-lumefantrine (artemether, 4 mg kg-1 body weight and lumefantrine, 24 mg kg-1 body weight). We found that therapeutic doses of the drugs did not change the levels of ovarian hydrogen peroxide (H2O2) and malondialdehyde (MDA), but increased uterine levels of H2O2 and MDA and reduced ovarian and uterine levels of reduced glutathione. In addition, whilst ovarian glutathione peroxidase (GPx) activity reduced in the lumefantrine monotherapy group, uterine GPx increased in the artemether monotherapy as well as the artemether-lumefantrine groups. Furthermore, the drugs reduced ovarian and uterine glutathione- S-transferase and uterine superoxide dismutase activities. The drugs reduced oestrogen level, whereas follicle-stimulating hormone was reduced by lumefantrine and artemether-lumefantrine therapies. Additionally, artemether and lumefantrine monotherapies significantly increased prolactin and progesterone levels compared with the control ( p < 0.05). The results suggest that in the absence of malarial parasite infection, the drugs induced oxidative stress in the ovary and uterus and disrupt hormonal balance in the rats.

In Vitro Antioxidant Properties of Methanolic Leaf Extract of Vernonia Amygdalina Del.

Various methods employed in evaluating antioxidant activities of various samples gives varying results depending on the specificity of the free radical or oxidant used as a reactant. This study investigated the antioxidant /radical scavenging properties of the methanolic extract of Vernonia amygdalina (MEVA) leaves and studied the relationship between the assay methods. Antioxidant capacity of MEVA was evaluated by measuring the radical scavenging activity (RSA) of MEVA on 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), nitric oxide (NO) and hydrogen peroxide (HP), hydroxyl radical (OH•) scavenging activity (HRSA), lipid peroxidation inhibition activity (LPIA) against 2,2,-azobis(2-amidinopropane) hydrochloride (AAPH) and Trolox Equivalent Antioxidant Capacity (TEAC) of MEVA against 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+) radicals as well as the reducing power (RP). Assay methods were subjected to regression analysis and their correlation coefficients calculated. Results were analysed using student?s t-test and ANOVA. MEVA exhibited highest percentage RSA of 85.8% on HP, followed by DPPH• (29.6%), OH• (26.4%) and least on NO• (21.8%). MEVA inhibited AAPH-induced lipid peroxidation by 30.0% and ABTS-induced radical by 1489% with a marked RP of 0.242±0.01. DPPH correlated excellently with RP (r2 = 0.86), TEAC (r2 = 0.94) and HRSA (r2 = 0.89), the four having good relationship with each other, while LPIA correlated moderately with HP (r2 = 0.48 and NO (r2 = 0.34). MEVA exhibited significant free radical scavenging and antioxidant activities. The assay methods correlates very well and could therefore be employed for investigating and understanding antioxidant properties and scavenging activities of plant materials.

Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats.

We investigated the toxic effect of nevirapine (NVP; Viramune(®)), an antiretroviral drug, on the liver, kidney and testis of Wistar rats. Twenty-one rats were assigned into 3 groups of 7 animals each. The first group served as control, and the second and third groups received NVP at 18 and 36 mg/kg body weight, respectively. Clinical signs of toxicity were not observed in the animals. NVP at both doses did not significantly (p > 0.05) alter the body weight gain, relative weights of kidney and testis, serum protein, urea, creatinine and alkaline phosphatase levels of the animals. However, NVP2 significantly (p < 0.05) increased the relative weight of liver, level of serum total bilirubin and activities of γ-glutamyl transferase, alanine and aspartate aminotransferases. NVP administration caused a dose-dependent, significant (p < 0.05) elevation of lipid peroxidation measured as malondialdehyde (MDA) content in the liver, kidney and testis of the rats. Hepatic, renal and testicular MDA were increased by 107%, 80% and 163%, respectively, in NVP2-treated rats. Elevation in MDA was accompanied by a significant (p < 0.05) decrease in the activities of hepatic, renal and testicular superoxide dismutase and catalase. NVP2 caused 43% and 32% decrease in spermatozoa motility and live/dead sperm count, respectively, and 94% increase in total sperm abnormalities. Histopathological findings showed that NVP2 caused degeneration of seminiferous tubules in testis, and severe necrosis in liver slides. NVP induced oxidative stress with corresponding decrease in antioxidant status of the rats. The changes in sperm parameters and, elevation of liver marker enzymes suggest an interference of NVP2 with these organs.

Evaluation of antioxidant properties of Mallotus oppositifolium in in-vitro, in-vivo and ex-vivo model systems.

The protective effect of antioxidants and naturally occurring substances against oxidative stress damage has recently attracted much attention. The leaves of Mallotus oppositifolium, a shrub of the family Euphorbiacea that grows in many parts of Africa, are used in folk medicine and herbal preparations for the treatment of dysentery, worms and malaria. The study investigated the antioxidant properties of the methanolic extract of the leaves of Mallotus oppositifolium (MEMO) in comparison with butylated hydroxyl anisole (BHA) as a standard antioxidant using three free radical generators viz hydrophilic radical generator 2,2-azobis(2-amidino propane) dihydrochloride (AAPH), hydrophobic radical generator 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN) and hydroxyl radical and non-specific radical generator Fe2+/ascorbate system in an in vitro, in vivo and ex-vivo model systems. Phytochemical analysis of the leaves extract was also assessed. Phytochemical analysis of the powdered leaves revealed the presence of alkaloids, tannins, cardenolides and saponins. In vitro study indicated that while MEMO failed to inhibit lipid peroxidation (LPO) induced by AAPH, while BHA offered 55.5% inhibition. In addition, while AMVN-induced LPO was inhibited by 17.7% and 29.4% by MEMO and BHA respectively, Fe2+/ascorbate system-induced LPO was inhibited by 57.9% and 78.9% by MEMO and BHArespectively. Ex-vivo studies showed that MEMO at 100mg/kg bw reduced malondialdehyde and protein carbonyl levels by 34.5% and 12.0% respectively compared with the control. In vivo, MEMO increased (P<0.05) superoxide dismutase and catalase activities by 408.0% and 295.0% respectively. Taken together, this study demonstrates that MEMO exhibits antioxidant, radical scavenging and enhancement of enzymatic antioxidant capacity and as such could intervene in toxicological processes mediated by free radical mechanisms.

N-acetylcysteine pretreatment ameliorates mercuric chloride-induced oxidative renal damage in rats.

The effectiveness of the antioxidant thiol, N-acetylcysteine (NAC), in enhancing methylmercury (CH3HgCl) excretion and its utility as a possible antidote in CH3HgCl poisoning has been reported. NAC, however, has been reported to be ineffective in accelerating excretion of divalent toxic metals, including inorganic mercury, Hg2+. In this study, we evaluated the possible protective effect of short-term pretreatment with NAC against mercuric chloride (HgCl2) toxicity in rat model. This is aimed at determining its chemopreventive or prophylactic benefit in situations of high risk exposure (occupational/industrial) to mercury. Rats were divided into three treatment groups. Group I received saline (10 ml/kg) and served as control. Group II received HgCl2 (5mg/kg) and group III received NAC (10mg/kg) plus (5mg/kg). All administration was via intraperitoneal (i.p.) injection. Saline and NAC were administered for 5days and HgCl2 was administered to rats in groups II and III on the 5th day. Animals were sacrificed 24 hours after HgCl2 injection and samples obtained for biochemical evaluation. Results revealed that single i.p. injection of HgCl2 induced significant renal oxidative damage resulting in significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), depletion of reduced glutathione (GSH) and increase in malondialdehyde (MDA) levels in these rats. The activities of glucose-6-phosphatase (G6Pase) and 5'-nucleotidase (5'-NTD) (markers of microsomal damage) also decreased in these HgCl2 treated rats. The oxidative damage induced by HgCl2 led to significant alterations in renal histology and caused functional impairment (indicated by elevated blood urea nitrogen (BUN) and serum creatinine) in these rats. NAC was effective in attenuating the oxidative damage, functional impairments and histopathological changes that characterized HgCl2 intoxication in this study. Renal antioxidant defense system was re-enforced by NAC, leading to increase in the activities of SOD, CAT, GST and decreases in GSH depletion and MDA level. Our results therefore reveal the ameliorative effect of NAC pretreatment against HgCl2 toxicity in vivo, thus, suggesting its usefulness as a possible chemoprophylactic agent during occupational or industrial exposure to inorganic mercury.

Hibiscus sabdariffa ethanolic extract protects against dyslipidemia and oxidative stress induced by chronic cholesterol administration in rabbits.

Excessive intake of cholesterol (CHOL) and induction of free radical production play a critical role in the pathophysiology of several human diseases. Dietary therapy with plant products rich in flavonoids has been shown to provide benefits without the adverse effects of agents used in clinical practice. Hibiscus sabdariffa (HS) has been used for various purposes due to myriads of flavonoids present in it. In this study, the chemopreventive property of HS ethanolic extract (HSE) was investigated in dyslipidemia and oxidant stress associated with prolonged CHOL administration in rabbits. Twenty-five (25) adult male rabbits weighing between 1.5 and 1.7 kg were used and randomly divided into five groups of five rabbits per group. The CHOL-fed rabbits received 1 g/kg/day of CHOL suspended in 1 ml of corn oil for 8 weeks. Group 1 received 1 ml of corn oil and served as control. Group 2 was fed with CHOL only while groups 3, 4 and 5 received daily doses ofcholestyramine (questran, 260 mg/kg), HSE 200 mg/kg and HSE 300 mg/kg respectively along with CHOL. Animals were sacrificed by cervical dislocation 24-hours after last dose. Enzymic and non-enzymic markers of oxidative stress and lipid profile were analysed in serum, liver, kidney and heart of rabbits. HSE significantly attenuated the alteration in lipid levels and antioxidant status induced by high CHOL intake in rabbits in this study. Both serum and tissue levels of low density lipoprotein-CHOL, triglycerides, phospholipids, and total CHOL decreased with increase in high density lipoprotein-CHOL except in the heart, following treatment with HSE in CHOL-fed rabbits when compared with the untreated group (p<0.05). Similarly, HSE prevented CHOL-induced depletion of enzymic (superoxide dismutase, catalase) and non-enzymic (reduced glutathione, vitamin C) antioxidants with the attendant increases in lipid peroxidation and xanthine oxidase activity in these animals. The effectiveness of HSE in this condition was comparable with that of cholestyramine but with greater in potency. Data from this study demonstrate the hypolipidaemic and antioxidant activities of HSE and suggest its therapeutic potential in disorders of lipid metabolism and cardiovascular events associated with hypercholesterolemia.

Concentrations of copper, iron, and zinc in the major organs of the wistar albino and wild black rats: a comparative study.

The concentrations of copper, iron, and zinc in the major organs of Wistar albino (Rattus norvegicus) and wild black rats (Rattus rattus) were measured by means of atomic absorption spectroscopy. The copper levels in the kidneys and liver of the Wistar albino rats (WARs) were significantly higher (p<0.05) than in the wild black rats (WBRs). There were no significant differences in the concentrations of zinc in the liver, lungs, kidneys, and brain between the two study groups, but zinc was significantly higher in the spleen (p<0.05) and lower in the heart (p<0.05) of WAR, compared to WBRs. Iron was significantly higher (p<0.05) in the heart and spleen of WBRs, compared to WARs. There were no extreme differences in the organ concentrations of trace elements between the two species, but, cumulatively, the WARs tend to have higher metallic concentrations in their system than the WBRs. The potential of these differences on the experimental results should not be overlooked and will serve as basis to further consider the complex interrelationships of these animals in their microenvironments and macroenvironments.