Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms

被引:28
作者
Kushwaha, S. [1 ]
Jena, G. B. [1 ]
机构
[1] Natl Inst Pharmaceut Educ & Res, Facil Risk Assessment & Intervent Studies, Dept Pharmacol & Toxicol, Sect 67, Sas Nagar 160062, Punjab, India
关键词
Comet assay; Diabetes; DNA damage; Enalapril; Oxidative stress; Sperm; Testes; MALE REPRODUCTIVE FUNCTION; OXIDATIVE STRESS; DNA-DAMAGE; ANGIOTENSIN-II; MOLECULAR-MECHANISMS; LIPID-PEROXIDATION; SEXUAL DYSFUNCTION; HUMAN SPERMATOZOA; RELATIVE IMPACT; ACE-INHIBITORS;
D O I
10.1007/s00210-011-0707-x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Diabetes mellitus, a state of persistent hyperglycemia, is a major cause of micro- and macrovascular diseases. It affects nearly every system in the body including the reproductive system. Abnormalities in spermatogenesis and sexual function have been documented in animal models for both types of diabetes. The purpose of the present study is to determine the possible protective effects of enalapril against the germ cell toxicity in diabetic rat. Sprague-Dawley rats were divided into four groups: (1) control, (2) control + enalapril, (3) diabetic, and (4) diabetic + enalapril. Enalapril was administered per orally for 4 and 8 weeks continuously. After the treatment, animals were sacrificed and blood glucose level, sperm count, sperm DNA damage, apoptotic cell death, immunohistochemistry of 8-oxo- 7,8-dihydro- 2'-deoxyguanosine, and the cellular toxicity were performed. Furthermore, western blotting was performed to evaluate the expression of NF kappa B and COX-2 in testes. The results of the present study indicate that intervention of enalapril ameliorates the sperm DNA damage, reduces the oxidative stress, and down-regulates the expression of NF kappa B and COX-2 expression in streptozotocin-induced diabetic rat.
引用
收藏
页码:111 / 124
页数:14
相关论文
共 62 条
[41]  
Neeraja S, 2003, Reprod Biomed Online, V6, P302
[42]   Diabetic rat testes: morphological and functional alterations [J].
Ricci, G. ;
Catizone, A. ;
Esposito, R. ;
Pisanti, F. A. ;
Vietri, M. T. ;
Galdieri, M. .
ANDROLOGIA, 2009, 41 (06) :361-368
[43]   Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase [J].
Rossi, A ;
Kapahi, P ;
Natoli, G ;
Takahashi, T ;
Chen, Y ;
Karin, M ;
Santoro, MG .
NATURE, 2000, 403 (6765) :103-108
[44]   Oxidative stress in mature rat testis and its developmental changes [J].
Sakai, Yasuhiro ;
Aminaka, Masahito ;
Takata, Ayako ;
Kudou, Yuichiro ;
Yamauchi, Hiroshi ;
Aizawa, Yoshiharu ;
Sakagami, Hiroyuki .
DEVELOPMENT GROWTH & DIFFERENTIATION, 2010, 52 (07) :657-663
[45]   Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions [J].
Savoia, Carmine ;
Schiffrin, Ernesto L. .
CLINICAL SCIENCE, 2007, 112 (7-8) :375-384
[46]   Sexual behaviour, sperm quantity and quality after short-term streptozotocin-induced hyperglycaemia in rats [J].
Scarano, W. R. ;
Messias, A. G. ;
Oliva, S. U. ;
Klinefelter, G. R. ;
Kempinas, W. G. .
INTERNATIONAL JOURNAL OF ANDROLOGY, 2006, 29 (04) :482-488
[47]   Angiotensin II Induces DNA Damage in the Kidney [J].
Schmid, Ursula ;
Stopper, Helga ;
Schweda, Frank ;
Queisser, Nina ;
Schupp, Nicole .
CANCER RESEARCH, 2008, 68 (22) :9239-9246
[48]   Molecular mechanisms of high glucose-induced cyclooxygenase-2 expression in monocytes [J].
Shanmugam, N ;
Gonzalo, ITG ;
Natarajan, R .
DIABETES, 2004, 53 (03) :795-802
[50]  
SOWERS JR, 1994, HYPERTENSION, V23, P145