PMID- 30772502
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20190827
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Linking)
VI  - 86
DP  - 2019 May 1
TI  - Effect of long-term sodium nitrate administration on diabetes-induced anemia and 
      glucose homeostasis in obese type 2 diabetic male rats.
PG  - 21-30
LID - S1089-8603(18)30354-9 [pii]
LID - 10.1016/j.niox.2019.02.003 [doi]
AB  - PURPOSE: Anemia is common in patients with type 2 diabetes. This aims at 
      determining long-term effects of nitrate administration on diabetes-induced 
      anemia in obese type 2 diabetic rats. METHODS: Male Wistar rats were divided into 
      4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Type 2 
      diabetes was induced using high-fat diet followed by injection of streptozotocin 
      (30 mg/kg). Sodium nitrate (100 mg/L in drinking water) was administered for six 
      months. After overnight fasting, levels of glucose and erythropoietin (EPO) and 
      complete blood cell count (CBC) were measured at month 0, month 3, and month 6. 
      At month 6, serum iron, and testosterone as well as EPO protein levels and 
      hypoxia-inducible factor-1 (HIF-1) mRNA levels in kidney and liver were measured. 
      RESULTS: Nitrate administration decreased serum glucose in diabetic rats by 10% 
      and 15% at months 3 and 6, respectively. Nitrate restored decreased red blood 
      cells count, hemoglobin concentration, and hematocrit to control levels in 
      diabetic rats; in addition, nitrate restored decreased serum, kidney, and liver 
      EPO levels to near normal values. Nitrate also increased HIF-1 mRNA levels in 
      both kidney and liver of diabetic rats. Diabetic rats had lower serum 
      testosterone (37%) and iron (20%) and nitrate restored these parameters to near 
      normal values. CONCLUSION: Long-term and low dose of nitrate had beneficial 
      effects against anemia in obese type 2 diabetic rats; these effects were 
      associated with increased EPO and HIF-1 levels in kidney and liver as well as 
      increased circulating EPO, testosterone, and iron.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Khorasani, Vajiheh
AU  - Khorasani V
AD  - Endocrine Physiology Research Center, Research Institute for Endocrine Sciences. 
      Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of 
      Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
FAU - Jeddi, Sajad
AU  - Jeddi S
AD  - Endocrine Physiology Research Center, Research Institute for Endocrine Sciences. 
      Shahid Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Yaghmaei, Parichehr
AU  - Yaghmaei P
AD  - Department of Biology, Science and Research Branch, Islamic Azad University, 
      Tehran, Iran.
FAU - Tohidi, Maryam
AU  - Tohidi M
AD  - Prevention of Metabolic Disorders Research Center, Research Institute for 
      Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Ghasemi, Asghar
AU  - Ghasemi A
AD  - Endocrine Physiology Research Center, Research Institute for Endocrine Sciences. 
      Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: 
      Ghasemi@endocrine.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190214
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Blood Glucose)
RN  - 0 (EPO protein, human)
RN  - 0 (Hemoglobins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Nitrates)
RN  - 0 (RNA, Messenger)
RN  - 11096-26-7 (Erythropoietin)
RN  - 3XMK78S47O (Testosterone)
RN  - 5W494URQ81 (Streptozocin)
RN  - 8M4L3H2ZVZ (sodium nitrate)
RN  - 9007-73-2 (Ferritins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Administration, Oral
MH  - Anemia/*drug therapy/etiology
MH  - Animals
MH  - Blood Glucose/*metabolism
MH  - Diabetes Mellitus, Experimental/chemically induced/complications
MH  - Diabetes Mellitus, Type 2/chemically induced/complications
MH  - Erythrocyte Count
MH  - Erythropoietin/metabolism
MH  - Ferritins/metabolism
MH  - Hematocrit
MH  - Hemoglobins/metabolism
MH  - Homeostasis/*drug effects
MH  - Hypoxia-Inducible Factor 1/genetics/metabolism
MH  - Iron/metabolism
MH  - Male
MH  - Nitrates/administration & dosage/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats, Wistar
MH  - Streptozocin
MH  - Testosterone/metabolism
OTO - NOTNLM
OT  - Anemia
OT  - Complete blood cell count
OT  - Erythropoietin
OT  - Hypoxia-inducible factor-1
OT  - Iron
OT  - Nitrate
OT  - Nitric oxide
OT  - Testosterone
OT  - Type 2 diabetes
EDAT- 2019/02/18 06:00
MHDA- 2019/08/28 06:00
CRDT- 2019/02/18 06:00
PHST- 2018/11/26 00:00 [received]
PHST- 2019/02/04 00:00 [revised]
PHST- 2019/02/13 00:00 [accepted]
PHST- 2019/02/18 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2019/02/18 06:00 [entrez]
AID - S1089-8603(18)30354-9 [pii]
AID - 10.1016/j.niox.2019.02.003 [doi]
PST - ppublish
SO  - Nitric Oxide. 2019 May 1;86:21-30. doi: 10.1016/j.niox.2019.02.003. Epub 2019 Feb 
      14.