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Deltamethrin-induced testicular apoptosis in rats: the protective effect of nitric oxide synthase inhibitor
M El-Gohary1, W M Awara, S Nassar
1Department of Forensic Medicine and Clinical Toxicology, College of Medicine, University of Tanta, Egypt.
Abstract:
This study is the first to examine and characterize the testicular apoptosis which might be induced due to exposure of male rats to deltamethrin. Furthermore, the role which might be played by nitric oxide (NO), as well as the other reactive oxygen species (ROS) in controlling this testicular apoptosis was assessed. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis and cellular morphology on testicular tissue sections. It was found that administration of deltamethrin (1 mg/kg daily for 21 days) to animals resulted in characteristic DNA migration patterns (laddering), thereby providing evidence that apoptosis is the major mechanism of cell death in the testicular tissues. In addition, histopathological examination of testicular tissue sections showed that apoptosis was confined to the basal germ cells, primary and secondary spermatocytes. These changes, in addition to the appearance of Sertoli cell vacuoles in deltamethrin-intoxicated animals, indicates the suppression of spermatogenesis. At the same time, the plasma levels of both NO and lipid peroxides measured as malondialdehyde (MDA) were found to be significantly increased in deltamethrin-treated animals. Administration of NO synthase (NOS) inhibitors such as N(G)-nitro monomethyl L-arginine hydrochloride (L-NMMA, 1 mg/kg) to rats 2 h before exposure to deltamethrin was effective in the reduction of the typically testicular apoptotic DNA fragmentation pattern and the associated histopathological changes. These findings may suggest that deltamethrin-induced testicular apoptosis is mediated by NO. Therefore, the pharmacological manipulation of apoptosis by selective NOS inhibitors such as L-NMMA may offer new possibilities for the control of deltamethrin-induced testicular dysfunction and infertility in the future.
Insights
Deltamethrin exposure induces testicular apoptosis in male rats, primarily affecting germ cells. Nitric oxide (NO) plays a key role in this process, suggesting NO synthase inhibitors could treat deltamethrin-induced infertility.
Area of Science:
- Toxicology
- Reproductive Biology
- Cellular Biology
Background:
- Pesticide exposure, specifically deltamethrin, is a growing concern for male reproductive health.
- Understanding the mechanisms of pesticide-induced testicular damage is crucial for developing effective treatments.
- Nitric oxide (NO) and reactive oxygen species (ROS) are implicated in various cellular processes, including apoptosis.
Purpose of the Study:
- To investigate deltamethrin-induced testicular apoptosis in male rats.
- To assess the role of nitric oxide (NO) in deltamethrin-induced testicular apoptosis.
- To explore the potential of nitric oxide synthase (NOS) inhibitors in mitigating deltamethrin's effects on male fertility.
Main Methods:
- Male rats were administered deltamethrin (1 mg/kg daily for 21 days).
- Apoptosis was evaluated using DNA fragmentation assays (agarose gel electrophoresis) and histopathological examination of testicular tissues.
- Plasma levels of NO and malondialdehyde (MDA) were measured.
- Rats were co-treated with a NOS inhibitor (L-NMMA) before deltamethrin exposure.
Main Results:
- Deltamethrin exposure induced significant DNA fragmentation, indicating apoptosis in testicular tissues.
- Histopathological analysis revealed apoptosis in germ cells and spermatocytes, along with Sertoli cell vacuolation, suggesting suppressed spermatogenesis.
- Plasma levels of NO and MDA were significantly elevated in deltamethrin-treated rats.
- Administration of L-NMMA reduced deltamethrin-induced DNA fragmentation and histopathological damage.
Conclusions:
- Deltamethrin induces testicular apoptosis in male rats, mediated by nitric oxide (NO).
- Spermatogenesis is suppressed following deltamethrin exposure.
- Pharmacological inhibition of NO synthesis using agents like L-NMMA shows promise in preventing deltamethrin-induced testicular dysfunction and infertility.

