EFFECT OF SELECTED FLAVONOIDS ON TESTICULAR DYSFUNCTION IN FRUCTOSE/STREPTOZOTOCIN-INDUCED DIABETIC RATS

Abstract

The main objective of this study was to investigate the effect of selected structurally related flavonoids (taxifolin, eriodictyol, rutin and quercetin) on testicular dysfunction in fructose/streptozotocin-induced diabetic rats. Type-2 diabetes mellitus (T2DM) was induced in adult male Wistar rats through intraperitoneal administration of 40 mg/kg streptozotocin to rats after 14 days of ad libitum feeding with 10% fructose solution. Confirmed diabetic animals (fasting blood glucose concentration ≥250 mg/dL) were post-treated with varying doses of taxifolin, eriodictyol, rutin and quercetin for 11 days and compared with normal and diabetic controls. At the end of the period of treatment, blood glucose concentration of animals was determined. Rats were sacrificed, testes and epididymides excised and blood samples collected and processed for biochemical estimations. Glycated haemoglobin (HBA1C) was estimated in the serum. Enzyme and non-enzyme biomarkers of testicular and epididymal oxidative stress were estimated in homogenates and reproductive hormones were determined in the serum of experimental animals. Testicular and epididymal expression of proinflammatory cytokines and androgenic genes were determined. Histopathological evaluation of testicular and epididymal tissues was carried out. Results indicated that serum concentrations of blood glucose and HBA1C which were increased in the diabetic control group were decreased in groups post-treated with flavonoids. In addition testicular and epididymal oxidative stress in the diabetic control group was ameliorated in groups post treated with the flavonoids. Also, decrease in serum hormone level occasioned by fructose feeding and streptozotocin injection in the diabetic control group was corrected in the flavonoids post treated groups. Decreased expression of testicular and epididymal pro-inflammatory cytokines and androgenic genes were observed in the diabetic control group, but this was ameliorated in the groups post-treated with the selected flavonoids. Histoarchitectural alterations observed in the diabetic control group were corrected in the flavonoids post-treated groups. Analysis of the results showed that taxifolin showed better activity than eriodictyol which was administered to rats at the same dose (0.25, 0.5 and 1.0 mg/kg b.w); while quercetin showed superior activity to rutin which was administered at the same dose to animals (5.0, 10.0, 20.0 mg/kg b.w). Structural considerations indicated that possession of 3-OH in taxifolin which is absent in eriodictyol might have contributed to its better activity while glycosylation of rutin could have contributed to its reduced bioactivity compared to quercetin. In conclusion taxifolin, eriodictyol, rutin and quercetin showed multi-mechanistic anti-type-2 diabetes mellitus activity and could show potentials in antidiabetic drug development.