EVALUATION OF PROLONGED ADMINISTRATION OF ARTEMETHER-LUMEFANTRINE ON SPERM INDICES AND TESTICULAR BIOMARKERS OF OXIDATIVE STRESS IN MALE WISTAR RATS: AMELIORATIVE EFFECT OF VITAMIN E.

EVALUATION OF PROLONGED ADMINISTRATION OF ARTEMETHER-LUMEFANTRINE ON SPERM INDICES AND TESTICULAR BIOMARKERS OF OXIDATIVE STRESS IN MALE WISTAR RATS: AMELIORATIVE EFFECT OF VITAMIN E.

Abstract:

There is frequent use of artemisinin-based combination therapies (ACTs) due to recurrence of malaria infection in Nigeria. The ACTs generate free radicals as part of their mode of action. Reactive oxygen species have been implicated in the etiology of male infertility. In this study, the effect of prolonged administration of artemether-lumefantrine (AL) and the ameliorative effect of vitamin E (VE) on testicular functions and biomarkers of oxidative stress was evaluated. Adult male Wistar rats (n = 35) were divided into five (5) groups of seven (7) rats each and treated as follows: Group I (control): 1ml/kg distilled water; group II: 1ml/kg olive oil; group III: 2.29 mg/13.74 mg/kg AL; group IV: 2.29 mg/13.74 mg/kg AL + 100 mg/kg of VE and group V: allowed to recover from treatment with AL for 2 weeks before sampling (2.29 mg/13.74 mg/kg AL + two weeks recovery). Administration was done orally twice daily for a period of two (2) weeks. At the end of the experiment, animals were sacrificed and the testes harvested and sperm indices, testicular testosterone and biomarkers of oxidative stress parameters determined. There was a remarkable but insignificant decrease in all sperm indices and testicular testosterone level in the AL group when compared with the control rats. However, a significantly (P < 0.05) higher percentage of sperm head defects was observed in the recovery than other groups. There was an insignificant increase in testicular malondialdehyde (MDA) level in the AL group when compared with other groups. Similarly, a remarkable but insignificant decrease in the level of testicular antioxidant enzyme, superoxide dismutase, but a significant (P < 0.05) decrease in the levels of catalase and glutathione peroxidase, was equally observed in the AL as compared with other groups. A remarkable but insignificant decrease in malondialdehyde and an increase in antioxidant enzymes, testosterone level, and sperm indices were observed in the vitamin E and recovery groups. It is therefore, concluded that prolonged administration of artemether-lumefantrine: (i) does not significantly affect most sperm indices (except sperm head morphology) and testicular testosterone concentration; (ii) induces significant alterations in testicular antioxidant enzymes activity suggestive of oxidative stress; (iii) and that vitamin E and ceazation of treatment with artemether-lumefantrine causes appreciable amelioration of the alterations in the biomarkers of oxidative stress.

EVALUATION OF PROLONGED ADMINISTRATION OF ARTEMETHER-LUMEFANTRINE ON SPERM INDICES AND TESTICULAR BIOMARKERS OF OXIDATIVE STRESS IN MALE WISTAR RATS: AMELIORATIVE EFFECT OF VITAMIN E.