An aminoglycoside antibiotic gentamycin induces oxidative stress, reduces antioxidant reserve and impairs spermatogenesis in rats

Abstract

-Gentamycin (GS) is an aminoglycoside antibiotic used to treat infections of various Gram-negative organisms. The present study was designed to investigate the effects of GS on oxidative stress, antioxidant levels, testicular structure and sperm parameters in the rat. Adult Wistar rats (12 week old; N=7/group) were treated (i. p.) with 0 mg/kg, 3 mg/kg and 5 mg/kg for 10 days at an interval of 24 hr between subsequent treatments. Animals were sacrificed on days 1 and 35 after the last treatment, and the reproductive organs were removed and weights of testis and seminal vesicle were recorded. The right testis was processed for light microscopic analysis. The left testis was homogenized and step 19 spermatids were counted to determine the daily sperm production (DSP) and daily abnormal sperm production (DASP). The sperm count, sperm motility and incidence of abnormal sperms were estimated in the epididymis. In testicular sections, along with the evaluation of qualitative changes, the seminiferous tubule diameter (STD) and the epithelial height (SE) were measured. The incidence of stage XIV tubules in testicular sections, meiotic figures and step 14 spermatids/stage XIV tubule, and step 19 spermatids/stage VII tubule were estimated. Intra-testicular levels of superoxide anion, lipid peroxidation and antioxidantssuperoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and ascorbic acid were measured. GS did not affect the body weight, but the testis weight and DSP were decreased at 5 mg/kg dose-level on both days (p<0.05), and the weight of seminal vesicle decreased on day 35 at both dose-levels. The DASP was increased in a dose-dependent manner (p<0.05) on days 1 and 35 at both dose-levels. The sperm count was decreased at both dose-levels on day 35, whereas the sperm motility was decreased and sperm abnormality was increased on day 1 at 5 mg/kg and on day 35 at both dose-levels. GS induced structural changes such as sloughing of seminiferous epithelium, vacuoles and gaps in the epithelium, nuclear pyknosis and atrophic changes in a few tubules. The tubular shrinkage was observed as indicated by decreased STD and SE on both days at 5 mg/kg dose-level. Incidence of stage XIV tubules and step 19 spermatids/stage VII tubule decreased on all time points at all dose-levels, whereas the step 14 spermatids and meiotic figures decreased on day 35 at both dose-levels (p<0.05). The free radical-superoxide anion concentration was significantly increased on day 1 in a dose-dependent pattern (p<0.05). However, activities of all 3 enzymatic antioxidants and ascorbic acid level decreased in a dose-dependent pattern on day 1 (p<0.05), except the GPx, which was also decreased on day 35 at 5 mg/kg dose-level. There was a significant rise in the thiobarbituric acid reactive substances on day 1 indicating increased lipid peroxidation in the testis. In conclusion, GS induces an oxidative stress-status in the testis by increasing free radical formation and lipid peroxidation, and by decreasing the antioxidant reserves...

Gentamisin’le Testis Hasarı Oluşturulan sıçanlarda C Vitamininin Koruyucu Etkisi Protective Effect of Vitamin C from Gentamicin Induced Testicular Damage in Rats.

“…Gentamisin testiste yapısal değişikliklere neden olmuş; epitelde dökülme, germ hücrelerinde dejenerasyon, seminifer tübüllerde atrofik değişiklikler, intersitiyel alanda boşluklar ve son olarak sperm üretiminde azalmaya neden olmuştur (5). Yaptığımız çalışmada da gentamisin grubunda benzer histopatolojik değişiklikler görülmüştür.…”

“…Gentamisinin ototoksik ve nefrotoksik olduğu iyi bilinmektedir. Gentamisin özellikle deney hayvanlarının testisinde yapısal değişikliklere neden olur epitelde dökülme, germ hücrelerinde dejenerasyon, seminifer tübüllerde atrofik değişiklikler, intersitiyel alanda boşluklar ve son olarak sperm üretiminde azalmaya neden olmaktadır (5). Oksidatif hasara ve nekroza neden olduğu bilinmektedir.…”

Vitamin C and oxidative stress in the seminiferous epithelium

“…So, vitamin C supplementation seems to improve semen quality (Sönmez et al, 2005) Gentamycin induces oxidative damage by increasing free radical formation, lipid peroxidation and by decreasing antioxidant levels. These effects were reversed following vitamin C supplementation, implying a direct role for this vitamin in protection against oxidative damage (Narayana, 2008). Also, some toxins as cisplatin, that decrease vitamin C levels, induce an increase of ROS and damage germ cells, with a signifi cant decline in sperm count (Narayana, 2008) and a higher incidence of DNA damage (Thiele et al, 1995).…”

Zamzam Water Ameliorates Oxidative Stress and Reduces HemoglobinA1c in Type 2 Diabetic Patients

“…The imbalance may result either form excessive exposure to pro-oxidants or from compromised antioxidant mechanisms. The later may result from deficiency of essential elements or from incapacitation of the antioxidant machinery through the pathologic insult of disease, while the earlier might emanate from exposure to exogenous toxins or the pathologic stress of disease [6,9]. Oxidative stress thus may occur in normal animals when antioxidant mechanisms are not working properly as in dietary deficiencies of vitamin E, vitamin C or the essential elements like selenium, zinc, and manganese among others.…”