Dose-dependent short-term study of di-n-butyl phthalate on the testicular antioxidant system of Wistar rats

Abstract

Di-n-butyl phthalate (DBP), a xenobiotic, is widely used in industries as a softener for polyvinyl chloride resins. The aim of the present study was to evaluate whether DBP induces oxidative stress in testes of Wistar rats. DBP at doses of 500, 1,000 and 1,500 mg/kg b.wt. (doses below LD50) was given orally for 7 days. After 24 hrs from the last dose, the animals were killed under ether anesthesia. Nonsignificant increase in testicular weight was observed. Histological studies indicated a dose-related degeneration of germinal, Leydig and Sertoli cells along with loss of spermatozoa in the lumen. The concentrations of malondialdehyde (TBARS), lipid hydroperoxides, water-soluble antioxidant capacity, glutathione-S-transferase, catalase and trace elements-zinc and copper increased while concentrations of total protein, lipid soluble antioxidant capacity, ascorbic acid, glutathione, total superoxide dismutase (SOD), Cu-ZnSOD, MnSOD, glutathione peroxidase, glutathione reductase and metallothionein decreased at all the dose levels. The data suggests that the cellular functions were adversely affected due to impairment of spermatogenesis indicative of oxidative stress as evident by altered antioxidative defense system which appears to mediate through hypothalamo-pituitary-gonadal axis. The spectrum of changes in testes reflects its susceptibility to phthalate even at low dose with the potential to interfere with critical reproductive function.

Ginger attenuated di (n-butyl) phthalate-induced reproductive toxicity in pubertal male rabbits

“…Moreover, phthalates downregulate the expression of genes required in cholesterol conveyance and testosterone synthesis in male rats (Thompson et al, 2005;Borch et al, 2006). Parallel to this, our results showed that DBP treatment reduced the serum (Nair et al, 2008;Nair, 2015) and testicular testosterone levels. Non-significant changes in the serum levels of LH and FSH were recorded during the 2 time points of study.…”

“…These findings were comparable to those described by Alam et al, (2010) and Bao et al, (2011). Nair et al (2008) and Nair (2015) stated similar histopathological results, although they reported atrophy of Leydig cells. Testicular lesions could be ascribed to the rise in MDA production and the resultant lipid peroxidation with advanced reduction in the various spermatogenic cells, as well as degeneration of Sertoli and Leydig cells.…”

“…This may be explained by using the low toxic dose of the DBP (520 mg/kg BW rabbit). Thus, Nair (2015) reported that rats treated 7 d with DBP at dose 500 mg/kg BW exhibited a non-significant reduction in testicular GPx levels, but it increased significantly at doses of 1000 and 1500 mg/kg BW. The balance between ROS and antioxidant enzymes in the male reproductive system is crucial for sperm health and survival.…”

“…The main possible mechanism of toxicity is based on the oxidative stress (Zhou et al, 2010). Several studies reported that DBP induced lipid peroxidation in rat testis (Wang et al, 2004 andNair, 2015).…”

Sulforaphane attenuates di-N-butylphthalate-induced reproductive damage in pubertal mice: Involvement of the Nrf2-antioxidant system

“…Testes are among the most susceptible organs to stress, heat and environmental pollutants . DBP at a dose of 500 mg/kg d, one‐sixteenth of the median lethal dose, is able to induce lesions in vivo but does not cause death . Our findings demonstrated that treatment with DBP at this dose resulted in apparent toxic effects, including anomalous development of the testes, severe atrophy of the seminiferous tubules and histological disruption of spermatogenesis, which could be attenuated by SFN supplementation.…”