ANTIPLASMODIAL AND CHEMOPREVENTIVE EFFECTS OF PAULLINIA PINNATA LINN. IN ETHYLENE GLYCOL MONOMETHYL ETHER - INDUCED TESTICULAR DYSFUNCTION IN RODENTS

Abstract

Malaria and infertility pose as threat to health where they are common globally. Paullinia pinnata (PP) is used in folkloric medicine to treat malaria and infertility but without scientific proof. In this study, the antiplasmodial activity of PP and its modulatory effects on ethylene glycol monomethyl ether (EGME)-induced testicular dysfunction were investigated in rodents. Ninety-six male Wistar rats (140-190g) were treated orally for sub-chronic toxicity (SCT) and chemopreventive studies (CS) with PP authenticated at Forestry Research Institute, Nigeria (FHI No.: I06555). Leaves of PP were air-dried, pulverized and extracted with absolute methanol by cold maceration. For SCT, 36 rats were assigned into 6 groups (n=6): Normal saline, PP(50, 100, 200, 400 and 800mg/kg). On day 29, rats were sacrificed and samples collected for biochemical analysis (BA). Serum alkaline phosphatase (ALP), total cholesterol (TC) and triglyceride were determined by spectrophotometry. In CS, 60 rats were used (6 groups, n=10) and treated with: Distilled water, 10% DMSO, EGME(200mg/kg), PP(200mg/kg), EGME+PP(100mg/kg), EGME+PP(200mg/kg). On day 22, rats were euthanized, levels of reproductive hormones and spermiogram were determined by ELISA and microscopy, respectively. Superoxide dismutase (SOD) and myeloperoxidase (MPO) were determined using spectrophotometry. For SCT and CS, histology of tissues (testes, brain, epididymes, liver, lung and kidney) was determined by microscopy. In the antiplasmodial studies, 102 Wistar mice (18- 27g) were inoculated with Plasmodium berghei NK 65. For curative test with safe dose (CTSD), infected mice (36) were allotted into 6 groups (n=6) and treated as follows: vehicle, untreatedinfected mice, chloroquine (CQ) (10mg/kg), artesunate (4mg/kg)-amodiaquine (10mg/kg) (ACT), PP(100mg/kg) and PP(200mg/kg) for 4 days and observed for 7 days postadministration. The animals were sacrificed and used for BA. Malaria aetiology profile was determined using microscopy. Data were subjected to descriptive statistics and ANOVA at α0.05. In SCT, PP (400, 800mg/kg) significantly increased ALP (29.0, 30.0%), PP (400mg/kg) significantly increased TC (25.0%) and triglycerides (47.0%) compared to controls. Safe dose of PP was 200mg/kg. For CS, rats with [EGME+PP100mg/kg] and [EGME+PP 200mg/kg] had significantly reduced testosterone (1.2±0.2; 1.1±0.6 vs 1.6±0.1pg/mL) and increased luteinizing hormone (13.5±1.5; 14.7±0.7 vs 10.0±0.0pg/mL), decreased sperm viability (11.0±1.0; 17.5±2.5 vs 70.0±3.9%), decreased motility (3.5±1.5; 10.0±2.9 vs 67.5±5.7%) and increased abnormality (14.0±0.4; 14.6±0.1 vs 11.9±0.3%). The [EGME+PP100mg/kg] and [EGME+PP 200mg/kg] significantly reduced SOD activities in the testes (U/mg protein) (5.0±1.7; 2.4±0.2 vs 9.5±0.0) and in the brain (7.1±1.4; 4.8±0.0 vs 12.3±1.1). In contrast, [EGME+PP100mg/kg] and [EGME+PP 200mg/kg] significantly increased MPO activities in the epididymes by 91.0 and 82.0% respectively. Percentage parasitaemia for CTSD were 42.5 and 36.3% for PP at 200 and 400 mg/kg, respectively. Histology showed severe germinal erosion in the testis for CS. Methanol leaf extract of Paullinia pinnata had anti-plasmodial activity but reduced chemopreventive effect on gonadal injury induced by ethylene glycol monomethyl ether.