Possible Mechanisms Underlying the Testicular Toxicity of Oxfendazole in Rats

Abstract

To clarify the mechanisms underlying the testicular toxicity of oxfendazole (OX), adult Wistar rats were orally administered a dose of 100 mg/kg/day for 3, 7, or 14 days. Assays of sex-related hormones showed a significant decrease in only the estradiol serum level at days 3 and 7, as compared with the control group. Histopathologically, marked degeneration of meiotic spermatocytes was observed in stage XIV-I seminiferous tubules from day 3 onwards, and these spermatocytes gave positive results on terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL). Abnormalities of spermiogenesis such as megakaryospermatids and binucleated spermatids were also observed in the testes of OX-treated rats. Under the electron microscope, lipid accumulation and dilatation of the endoplasmic reticulum were frequently found in the cytoplasm of the Sertoli cells on day 3. These results strongly suggest that OX induces both apoptosis of meiotic spermatocytes, most probably due to disruption of the microtubules, and degeneration of the Sertoli cells, characterized by distended endoplasmic reticulum and prominent cytosolic lipid accumulation.

Changes in Lipids Containing Long- and Very Long-Chain Polyunsaturated Fatty Acids in Cryptorchid Rat Testes1

“…Supporting evidence for the accumulation of neutral lipids in the latter may be found in the histologic observations presented by other authors, in which they show lipid droplets in the Sertoli cell cytoplasm under several pathological conditions that lead to spermatogenesis arrest [48,49]. This is consistent with the fact that damaged or dead germ cells are phagocytosed by Sertoli cells, which hydrolyze and are able to reutilize some of the resulting elements [50][51][52].…”

Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice

“…Mebendazole interacting with tubulin interferes with the assemblage of the mitotic apparatus in the parasite cells, thus causing a possible genotoxic activity leading to chromosomal malsegregation [29]. Also, Okamura et al [30] suggested that oxfendazole induces apoptosis of meiotic spermatocytes, most probably due to disruption of the microtubules, and degeneration of the Sertoli cells. Uppala et al [31] indicate that chemicals can induce cellular and chromosomal alterations, inducing early events in carcinogenesis.…”

The role of genomic instability and expression of the p53 protein gene network in the processes of oncogenesis in first- and second-generation children living in radioactively contaminated areas

“…По сведениям литературы, микроядра и протру-зии могут рассматриваться как биомаркеры канце-рогенного эффекта и быть самым ранним проявле-нием риска рака ротовой полости, лимфатических узлов, грудной клетки [18][19][20]. По нашим данным, максимальные кариологические (цитологические) изменения были выражены у матерей (1-е поколе-ние) с новообразованиями, в том числе злокаче-ственными (щитовидной железы, молочной железы) и перенесших оперативное лечение по поводу этих заболеваний.…”