PMID- 23648321
OWN - NLM
STAT- MEDLINE
DCOM- 20130905
LR  - 20220321
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 755
IP  - 1
DP  - 2013 Jul 4
TI  - Telmisartan ameliorates germ cell toxicity in the STZ-induced diabetic rat: 
      studies on possible molecular mechanisms.
PG  - 11-23
LID - S1383-5718(13)00115-0 [pii]
LID - 10.1016/j.mrgentox.2013.04.013 [doi]
AB  - Testicular damage is a common clinical problem in diabetic individuals that 
      severely affects the quality of life. The present study investigates the possible 
      protective mechanisms of telmisartan, an angiotensin II-receptor antagonist in 
      the germ cell of diabetic rat. Male SD rats were used and randomized into six 
      groups: control, telmisartan control, diabetic control and diabetic group treated 
      with telmisartan at the doses of 3, 6 and 12mg/kg/day, per oral for 4 weeks. 
      Diabetes was induced by injecting a single dose of streptozotocin (STZ), 
      (55mg/kg) dissolved in ice-cold 10mM citrate buffer; pH 4.4 and administered i.p. 
      immediately after preparation to the SD rats. At the end of the study, rats were 
      sacrificed and the levels of nitrite, superoxide, malondialdehyde (MDA), 
      glutathione (reduced and peroxidase) and superoxide dismutase (SOD) were 
      measured. Germ cell toxicity was evaluated by using sperm count, sperm comet 
      assay, histology of testes and terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL) assay. Further to confirm the oxidative and 
      nitrosative damage, immunohistological quantification of 8-oxo-dG 
      (8-oxo-7,8-dihydro-2'-deoxyguanosine) and 3-nitrotyrosine were evaluated 
      respectively. Results showed that telmisartan significantly restored the levels 
      of nitrite, superoxide, malondialdehyde, and glutathione and superoxide dismutase 
      in diabetic testes. Further, telmisartan significantly increased the sperm 
      counts, reduced apoptotic cell death, sperm DNA damage, oxidative and nitrosative 
      damage in diabetic rat. Western blot analysis showed that telmisartan reduced the 
      testicular inflammation and cell death by down-regulating the expression of 
      NF-kappaB, IL-6, TNF-alpha, p-ERK1/2, iNOS, caspase-3 and increasing the PPAR-gamma 
      expression. Results clearly indicate that telmisartan significantly reduced the 
      both oxidative and nitrosative stress, inflammation and cell death in diabetic 
      testes. The present results confirmed that telmisartan exhibited beneficial role 
      in the germ cell of diabetic rat.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Kushwaha, S
AU  - Kushwaha S
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research, Punjab, India. sapna.pharm@gmail.com
FAU - Jena, G B
AU  - Jena GB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130503
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoates)
RN  - 0 (Biomarkers)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - G9481N71RO (Deoxyguanosine)
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Angiotensin II Type 1 Receptor Blockers/*therapeutic use
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Benzimidazoles/*therapeutic use
MH  - Benzoates/*therapeutic use
MH  - Biomarkers/*analysis
MH  - Blotting, Western
MH  - DNA Damage/*drug effects
MH  - Deoxyguanosine/analogs & derivatives/analysis
MH  - Diabetes Mellitus, Experimental/chemically induced/metabolism/*prevention & 
      control
MH  - Germ Cells/cytology/*drug effects
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sperm Count
MH  - Telmisartan
MH  - Tyrosine/analogs & derivatives/analysis
OTO - NOTNLM
OT  - 8-oxo-7,8-dihydro-2'-deoxyguanosine
OT  - 8-oxo-dG
OT  - ARBs
OT  - AT1
OT  - Apoptosis
OT  - DNA damage, Diabetes
OT  - Germ cell
OT  - IL-6
OT  - Inflammation
OT  - NF-kappaB
OT  - PPAR-gamma
OT  - STZ
OT  - TNF-alpha
OT  - Telmi
OT  - Telmisartan
OT  - Testes
OT  - angiotensin II receptor type 1
OT  - angiotensin receptor blocker
OT  - iNOS
OT  - inducible nitric oxide
OT  - interleukin 6
OT  - nuclear factor kappa B
OT  - pERK
OT  - peroxisome proliferator-activated receptor gamma
OT  - phosphorylated extracellular-signal-regulated kinases
OT  - streptozotocin
OT  - telmisartan
OT  - tumor necrosis factor alpha
EDAT- 2013/05/08 06:00
MHDA- 2013/09/06 06:00
CRDT- 2013/05/08 06:00
PHST- 2012/12/25 00:00 [received]
PHST- 2013/03/27 00:00 [revised]
PHST- 2013/04/21 00:00 [accepted]
PHST- 2013/05/08 06:00 [entrez]
PHST- 2013/05/08 06:00 [pubmed]
PHST- 2013/09/06 06:00 [medline]
AID - S1383-5718(13)00115-0 [pii]
AID - 10.1016/j.mrgentox.2013.04.013 [doi]
PST - ppublish
SO  - Mutat Res. 2013 Jul 4;755(1):11-23. doi: 10.1016/j.mrgentox.2013.04.013. Epub 
      2013 May 3.