Gossypol

Gossypol (CAS 303-45-7) is a natural phenolic compound derived from the stems, leaves, seeds, and flower buds of cotton. As a PAF inhibitor, it exhibits antispermatogenic and anticancer activities and is commonly used to establish male infertility (oligo/azoospermia) animal models. Its molecular weight is 518.55 Da and it appears yellow. Its most common toxic effect is damage to the male and female reproductive systems; another important toxicity is interference with immune function, reducing animals' anti-infection capacity and vaccine efficacy[1].

In bovine granulosa cells, gossypol reduces hCG-induced cAMP formation in a dose-dependent manner. Gossypol (12.5 µg/ml) inhibits basal cAMP levels and progesterone secretion(2). Gossypol (50 and 100 µg/ml) reduces the percentage of sperm completing the swim-up process. When cultured with 5 or 10 µg/ml gossypol, development of cleaved embryos is reduced(3). In lymphocytes isolated from the lymph nodes of BALB/c mice, gossypol significantly inhibits proliferation of mouse lymphocytes stimulated by phorbol ester and ionomycin in a dose-dependent manner. Gossypol significantly inhibits lymphocyte transformation in both T-lymphocyte and B-lymphocyte subsets. Furthermore, gossypol induces lymphocyte apoptosis in a time- and dose-dependent manner(4).

In male Sprague-Dawley rats, intraperitoneal injection of gossypol (25 mg/kg) significantly alters the activities of hepatic and serum γ-glutamyltransferase (GGT) and microsomal monooxygenase(5). In rats, lower doses of gossypol (15 mg/kg/day for four weeks or 30 mg/kg/day for two weeks) cause marked morphological changes in the liver(6).

References: Gadelha I C N, Fonseca N B S, Oloris S C S, et al. Gossypol toxicity from cottonseed products[J]. The Scientific World Journal, 2014, 2014.

Lin Y C, Coskun S, Sanbuissho A. Effects of gossypol on in vitro bovine oocyte maturation and steroidogenesis in bovine granulosa cells[J]. Theriogenology, 1994, 41(8): 1601-1611.

Brocas C, Rivera R M, Paula-Lopes F F, et al. Deleterious actions of gossypol on bovine spermatozoa, oocytes, and embryos[J]. Biology of reproduction, 1997, 57(4): 901-907.

Xu W, Xu L, Lu H, et al. The immunosuppressive effect of gossypol in mice is mediated by inhibition of lymphocyte proliferation and by induction of cell apoptosis[J]. Acta Pharmacologica Sinica, 2009, 30(5): 597-604.

Deoras D P, Young-Curtis P, Dalvi R R, et al. Effect of gossypol on hepatic and serum γ-glutamyltransferase activity in rats[J]. Veterinary research communications, 1997, 21(5): 317-323.

Ying W, Hai-Peng L. Hepatotoxicity of gossypol in rats[J]. Journal of ethnopharmacology, 1987, 20(1): 53-64.