EFFECT OF METHYL JASMONATEON BENIGN PROSTATIC HYPERPLASIA INWISTAR RATS

Abstract

Benign ProstaticHyperplasia (BpH) is a progressive age-related disease. Currentdrugs used in the management of BpH have limited efficacy and many adverse effects, necessitating a continuous search for better options. Methyl Jasmonate (MeJa), a plant stress hormone, has been shown to be an anti-neoplastic agent via several mechanisms. However, its effect on BpH is unknown. This study was designed to assess the actions of MeJa in testosterone propionate (TP)-induced BpH in castrated rats. Castration of rats was performed by removing both testes through the scrotum sac under ketamine anesthesia. The BpH was induced by daily intraperitoneal injections of Tp at 3 mg/kg for 28 days.Forty eight Wistar rats (170 – 250g) were grouped into eight groups of six animals each as follows: non-castrated control, castrated (CAS) control, CAS + Tp, CAS + Tp + MeJa (50 mg/kg), CAS + Tp + finasteride (10 mg/kg), CAS + MeJa, CAS + finasteride, CAS + TP + MeJa + finasteride. Biochemical indices [alkaline phosphatase (ALP), acid phosphatase (ACP)and zinclevels] were determined by standard methods using a spectrophotometer. Antioxidant parameters [Superoxide Dismutase (SOD), Catalase, reduced Glutathione (GSH),Glutathione Peroxidase (GPx) and Lipid Peroxidation (LPO)]as well as inflammatory markers [Nitric Oxide (NO) and myeloperoxidase] were determined by standard methods using a spectrophotometer. Testosterone level was determined using ELISA. Lipid profile [Total Cholesterol (TC), Triglycerides and High Density Lipoprotein-Cholesterol (HDL-C)] were also determined spectrophotometrically. Prostate Specific Antigen (PSA), ki67, inducible Nitric Oxide Synthase (iNOS), Cyclooxygenase-2 (COX-2), p53, B-cell lymphoma (Bcl-2) and Bcl-2 associated X-protein (Bax) of the prostate were determined using immunohistochemistry. Histology of the prostate was performed using haematoxylin and eosinstaining. Data were analysed using ANOVA at α0.05. Administration of Tp significantly increased prostate weight (0.59±0.08 gvs 0.18±0.06 g) and its organo-somatic weights (0.07±0.02 vs 0.19±0.03) relative to castrated control. In BpH rats, the activities of ACPs (total, non-prostatic, prostatic) and ALP were increased by 455.1%, 766.0%, 274.4% and 522.2%, respectively. The levels of zinc and LPO increased by 19.8% and 38.6%, respectively. Treatment of BpH rats with MeJa decreased the activity of non-prostatic ACP, zinc and LPO levels by 34.2%, 32.5% and 62.1%, respectively. The levels of serum testosterone, prostatic NO and activity of myeloperoxidase were increased in BpH by 151.8%, 28.6% and 25.0%, respectively. Relative to castrated control, serum triglyceride (345.24±14.31 vs 240.74±12.12mg/dL) and TC (381.11±22.80 vs 281.76±2.30mg/dL) were increased, while HDL-C was decreased in BpH (276.87±8.62 vs 313.79±14.38mg/dL).The activities of antioxidant enzymes namely SOD (8.09±0.55 vs 12.08±0.73U/mg protein),Catalase (9.17±1.00 vs 19.57±0.94U/mg protein), GPx (1109.12±180.82 vs 1562.23±194.50U/mg protein) and GSH level (156.31±23.84 vs 249.04±23.48U/mg protein) were reduced in BpH relative to control. The MeJa improved the inflammatory, antioxidant, lipid profile and attenuated the expression of PSA, Ki67, iNOS, COX-2, Bcl-2, p53, Bax and histological architecture of the prostate in BpH. Methyl jasmonate attenuated testosterone propionate-induced benign prostatic hyperplasia in rats via induction of apoptosis, antioxidative and anti-inflammatory mechanisms.