Long-term bound gossypol administration damages the liver and reproductive functions of male mice

Gossypol is an anti-nutritional factor in cottonseed products, and its toxicity is reduced mainly by transforming free gossypol (FG) to bound gossypol (BG). However, the safety of BG chronic consumption in relation to liver and reproduction has not been fully examined. This study aimed to assess the effects of chronic BG exposure on liver and male reproductive function. BG with a purity of 97.38 % was prepared from whole egg solution and acetate gossypol, and its digestive stability was investigated by in vitro and in vivo digestion experiments. In vitro , digestion experiment of BG in the simulated gastric and intestinal fluid was performed. In vivo , thirty 8-week-old male C57BL/6 mice were randomly assigned into 3 groups, and the effects of BG on the liver and reproductive function of mice were studied by administering 24.8 mg/(kg·BW) BG (contains 0.67 mg FG) (marked as BG group), through gavage for 90 days, and administrated with 0.67 mg/(kg·BW) FG as a control group (C group), administrated with vehicle as a negative control group. Results show that BG dissociated into FG in simulated gastrointestinal environments. Long-term BG administration hindered the growth performance of the male mice, during which higher FG was detected in the feces of BG-administrated mice. This BG administration also increased serum alanine aminotransferase and aspartate aminotransferase levels, as well as the balloon degeneration and binucleate cells in the liver. Sperm concentration, sperm motility, epididymis coefficient, and the lactate dehydrogenase-X activity in the testis were inhibited by BG administration. Taken together, we reported that long-term administration with BG at a low dosage of 24.8 mg/(kg·BW) damages the growth performance, liver, and reproductive function, which may guide the modest use of cottonseed in foods and feeds.