Insecticide chlorpyrifos and fungicide carbendazim, common food contaminants mixture, induce hepatic, renal, and splenic oxidative damage in female rats.

The fungicide carbendazim (CBZ) and insecticide chlorpyrifos (CPF) are currently applied together by farmers for the control of pests. Here, we investigated the impacts of 7 days oral co-exposure to 10 mg/kg body weight of CPF and 50 mg/kg body weight of CBZ on selected oxidative stress and antioxidant biomarkers in the liver, kidney, and spleen of female rats. The results showed that while the body weight gain and relative organ weights were not significantly affected after separate exposure to CPF and CBZ, there was a significant decrease in the body weight gain with concomitant increases in the relative kidney and spleen weights of rats treated with the mixture. Also, CPF and CBZ co-exposure significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine ( p < 0.05) when compared with the groups treated with CBZ or CPF alone and the control. The significant decreases in both antioxidant enzymes activities and nonenzymatic antioxidant level following individual administration of CPF and CBZ to rats were intensified in the co-exposure group ( p < 0.05). Additionally, the marked increases in the levels of oxidative stress indices in liver, kidney, and spleen of rats treated with CPF or CBZ alone were intensified in the co-exposure group ( p < 0.05). Histopathologically, co-exposure to CPF and CBZ exacerbates their individual effects on the liver, kidney, and spleen. These findings showed that co-exposure to CPF and CBZ in rats elicited more severe oxidative damage on the liver, kidney, and spleen of the rats, indicative of an additive effect compared to CPF or CBZ alone and as such, may pose a greater environmental risk to humans.

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.

Artemisinin induces hormonal imbalance and oxidative damage in the erythrocytes and uterus but not in the ovary of rats.

Artemisinin is an antimalarial drug previously reported to induce neurotoxicity and embryotoxicity in animal models. This study investigated the erythrocytes and reproductive toxicity potentials of artemisinin in female rats. Animals were randomly divided into four study groups of eight rats each. The control group (group I) received corn oil, the vehicle, while groups II-IV were orally exposed to 7, 35 and 70 mg kg(-1) day(-1) of artemisinin, respectively, by gastric intubation for 7 consecutive days. Subsequently, we evaluated the impact of artemisinin on the endocrine environment and selected markers of oxidative damage and antioxidant status of the erythrocytes, ovary and uterus. Artemisinin significantly increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels and decreased catalase, glutathione peroxidase and superoxide dismutase activities in erythrocytes and uterus of rats compared with control group (p < 0.05). However, artemisinin did not alter ovarian MDA, H2O2, glutathione levels and catalase activity, while ovarian and uterine histological assessment revealed absence of visible lesions. Moreover, artemisinin significantly decreased follicle-stimulating hormone and increased progesterone levels compared with control (p < 0.05). Thus, these data suggest that in the absence of malarial parasite infection, artemisinin induced hormonal imbalance and oxidative damage in the erythrocytes and uterus but spared the ovary of rats.

Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin.

The indiscriminate use, abuse and patients' noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg(-1) artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg(-1) ) and overdose (35 mg kg(-1) ), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy.

Influence of coadministration of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative stress indices in female Wistar rats.

Among the artemisinin-based combination therapy (ACT) regimens, artemisinin derivative, artemether in combination with lumefantrine (artemether-lumefantrine, AL) has achieved excellent results in the fight against malarial scourge. In this study, we evaluated the toxic potential of these drugs at the therapeutic doses in female Wistar rats. Animals were randomly divided into four groups: those administered 1% Tween 80 (control), those administered artemether (4 mg/kg body weight), those administered lumefantrine (24 mg/kg body weight), and those coadministered artemether (4 mg/kg body weight) and lumefantrine (24 mg/kg body weight). The drugs were orally administered twice daily for 3 days by gastric intubation after which selected plasma biochemical indices, and erythrocytes antioxidant defence and lipid peroxidation markers were evaluated. Coadministration of artemether and lumefantrine raised liver and renal function markers and increased atherogenic index. While reduced glutathione, glucose-6-phosphate dehydrogenase (G6PD) and catalase activities were reduced, glutathione peroxidase and glutathione-s-transferase activities increased in all the treated groups compared to the control group. The drugs caused significant (p < 0.05) elevation of malondialdehyde (MDA) levels compared to the control group. These results imply that coadministration of artemether and lumefantrine may increase the risks of atherosclerosis as well as liver and renal function impairments in the users. In addition, the drugs may also promote oxidative stress in the erythrocytes.

Genetic diversity of Plasmodium falciparum field isolates from south western Nigeria.

BACKGROUND: Plasmodium falciparum the main causative agent of malaria is an important public health vector. With the use of PCR, its genetic diversity has been extensively studied with dearth information from Nigeria. METHODS: In this study, 100 P. falciparum strains merozoite surface protein 1(msp-1), merozoite surface protein 2 (msp-2) and Glutamate rich protein (Glurp) from Ogun State General Hospitals were characterized. The genetic diversity of P. falciparum isolates was analyzed by restriction fragment length polymorphism following gel electrophoresis of DNA products from nested polymerase chain reactions (PCR) of their respective allelic families KI, MAD 20, RO33 (MSP-1);FC27, 3D7 (MSP-2) and Glutamate rich protein respectively. RESULTS: Majority of the patients showed monoclonal infections while multiplicity of the infection for msp-1 and msp-2 were 1.1 and 1.2 respectively. The estimated number of genotypes was 8 msp-1 (4 KI; 3 MAD; 1 RO33) and 6 msp-2 (3 FC27; 3 3D7). 80% of the isolates coded for Glurp with allelic size ranged between 700 and 900 bp. CONCLUSION: The allelic distributions however were similar to those previously reported in other endemic malaria countries. Future studies will be designed to include other malaria endemic regions of Nigeria such as the oil exploration regions.