Abstract
Gentamicin (GM) is an aminoglycoside that has harmful effects on the male germ cells and sperm quality. N-3 polyunsaturated fatty acids (n-3 PUFA) are natural antioxidants that influence cell signaling and inflammation. Heme-oxygenase-1 (HO-1) and heat shock proteins (HSP) aid in cellular protection against cellular insults. This study aimed to explore the potential alleviating influences of treatment with n-3 PUFA on GM-induced testicular damage. Thirty-two albino male rats were divided into four equal groups. (1) The control group received normal saline, (2) the n-3 PUFA group received 100 mg/kg body weight/day n-3 PUFA daily for 4 weeks, (3) the GM group received 100 mg/kg/day GM intraperitoneally for 10 consecutive days, and (4) the GM + n-3 PUFA group received intraperitoneal GM for ten days followed by treatment with n-3 PUFA for 4 weeks. Significant reductions in sperm motility, viability, serum testosterone, total testicular protein, and germinal epithelium height were observed in the GM-treated group, with upregulation of the oxidative stress markers, HO-1 mRNA, and HSP70, and downregulation of proliferating cell nuclear antigen (PCNA). We also observed cellular disorganization, vacuolation, tubular distortion, and a significantly higher percentage of collagen. Ultra-structurally, most of the spermatogenic cells were electron dense and degenerated with rarefied cytoplasm. Treatment with n-3 PUFA resulted in a significant increase in sperm motility, viability, serum testosterone, and in the germinal epithelium height. Upregulation of HO-1 mRNA, HSP70, and PCNA expression and a significant reduction in the oxidative stress index were also observed. The findings confirm the potential ameliorative role of and imply novel mechanisms by which n-3 PUFA protects against GM-induced testicular injury. Key words: Polyunsaturated fatty acids, gentamicin, oxidative stress, testis, male infertility.  
Highlights
IntroductionThree of the most well-known among them, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are considered strong intracellular and intercellular mediators (Ambrozova, Pekarova et al 2010)
Rats treated with GM demonstrated a significant reduction in testis weight compared to those of rats in the control and n-3 PUFA groups (P
This study demonstrated a remarkable increase in the HO-1 mRNA expression level in GM-treated rats compared to the level in the control and n-3PUFA groups
Summary
Three of the most well-known among them, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are considered strong intracellular and intercellular mediators (Ambrozova, Pekarova et al 2010). They play a fundamental role in cell metabolism, signaling, and inflammation (Attuwaybi et al 2004, Vaughan, GarciaSmith et al 2012) and are capable of reducing lipid levels, blood pressure, thrombosis and reactive oxygen species (ROS) production, and the modulation of nitric oxide production (Demaison and Moreau 2002)
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