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
[1]   The role of free radicals and antioxidants in reproduction [J].
Agarwal, A ;
Gupta, S ;
Sikka, S .
CURRENT OPINION IN OBSTETRICS & GYNECOLOGY, 2006, 18 (03) :325-332
[2]   Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach [J].
Agarwal, A ;
Said, TM .
BJU INTERNATIONAL, 2005, 95 (04) :503-507
[3]   Insulin dependant diabetes mellitus: implications for male reproductive function [J].
Agbaje, I. M. ;
Rogers, D. A. ;
McVicar, C. M. ;
McClure, N. ;
Atkinson, A. B. ;
Mallidis, C. ;
Lewis, S. E. M. .
HUMAN REPRODUCTION, 2007, 22 (07) :1871-1877
[4]   Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa [J].
Aitken, RJ ;
Gordon, E ;
Harkiss, D ;
Twigg, JP ;
Milne, P ;
Jennings, Z ;
Irvine, DS .
BIOLOGY OF REPRODUCTION, 1998, 59 (05) :1037-1046
[5]   Hydroxy-2-deoxy-guanosine identifies oxidative DNA damage in a rural prediabetes cohort [J].
Al-Aubaidy, Hayder A. ;
Jelinek, Herbert F. .
REDOX REPORT, 2010, 15 (04) :155-160
[6]   AT1 receptors and L-type calcium channels:: functional coupling in supersensitivity to angiotensin II in diabetic rats [J].
Arun, KHS ;
Kaul, CL ;
Ramarao, P .
CARDIOVASCULAR RESEARCH, 2005, 65 (02) :374-386
[7]  
BAIN SC, 1991, J HUM HYPERTENS, V5, P511
[8]   Protective effect of enalapril on vascular reactivity of the rat aorta [J].
Baluchnejadmojarad, T ;
Roghani, M ;
Imani, A .
VASCULAR PHARMACOLOGY, 2004, 40 (06) :301-307
[9]  
Blankfield RP, 2002, NEW ENGL J MED, V346, P705
[10]   METABOLISM AND TESTICULAR TOXICITY OF 1,3-DINITROBENZENE IN RATS OF DIFFERENT AGES [J].
BROWN, CD ;
FORMAN, CL ;
MCEUEN, SF ;
MILLER, MG .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1994, 23 (03) :439-446