Protective effect of intermediate doses of hydrogen sulfide against myocardial ischemia-reperfusion injury in obese type 2 diabetic rats
(2020) In Life Sciences 256.- Abstract
Objective: Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H2S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. Methods: T2D was induced using a high-fat diet (HFD) and low-dose of streptozotocin. Rats were divided into control, T2D, and T2D + NaSH groups. NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg) was administered intraperitoneally for 9 weeks. At the end of the study, heart from all rats were isolated and left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV... (More)
Objective: Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H2S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. Methods: T2D was induced using a high-fat diet (HFD) and low-dose of streptozotocin. Rats were divided into control, T2D, and T2D + NaSH groups. NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg) was administered intraperitoneally for 9 weeks. At the end of the study, heart from all rats were isolated and left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV pressure (±dp/dt) were recorded during baseline and following myocardial IR injury. In addition, infarct size as well as mRNA expression of H2S- and nitric oxide (NO)-producing enzymes were measured. Results: In diabetic rats, NaSH only at doses of 0.56 and 1.6 mg/kg increased recovery of LVDP (16% and 42%), +dp/dt (25% and 35%) and –dp/dt (23% and 32%) as well as decreased infarct size (44% and 35%). At these doses, NaSH increased expressions of cystathionine γ-lyase (CSE) (440% and 271%) and endothelial NO synthase (eNOS) (232% and 148%) but it decreased the expressions of inducible NOS (iNOS) (55% and 71%). NaSH at 0.28, 2.8 and 5.6 mg/kg had no significant effects on these parameters. Conclusion: NaSH had a bell-shaped cardioprotective effect against myocardial IR injury in rats with T2D. Higher tolerance to IR injury in heart isolated from type 2 diabetic rats treated with intermediate doses of NaSH is associated with higher CSE-derived H2S and eNOS-derived NO as well as lower iNOS-derived NO.
(Less)
- author
- Jeddi, Sajad ; Gheibi, Sevda LU ; Kashfi, Khosrow ; Carlström, Mattias and Ghasemi, Asghar
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- HS-producing enzymes, Hydrogen sulfide, Infarct size, Ischemia-reperfusion injury, NO-producing enzymes, Type 2 diabetes
- in
- Life Sciences
- volume
- 256
- article number
- 117855
- publisher
- Elsevier
- external identifiers
-
- scopus:85086115734
- pmid:32473245
- ISSN
- 0024-3205
- DOI
- 10.1016/j.lfs.2020.117855
- language
- English
- LU publication?
- yes
- id
- 22731640-879a-4923-b67c-cc5df09996cc
- date added to LUP
- 2020-06-30 08:27:18
- date last changed
- 2024-03-04 21:50:49
@article{22731640-879a-4923-b67c-cc5df09996cc,
abstract = {{<p>Objective: Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H<sub>2</sub>S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. Methods: T2D was induced using a high-fat diet (HFD) and low-dose of streptozotocin. Rats were divided into control, T2D, and T2D + NaSH groups. NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg) was administered intraperitoneally for 9 weeks. At the end of the study, heart from all rats were isolated and left ventricular developed pressure (LVDP) and the peak rates of positive and negative changes in LV pressure (±dp/dt) were recorded during baseline and following myocardial IR injury. In addition, infarct size as well as mRNA expression of H<sub>2</sub>S- and nitric oxide (NO)-producing enzymes were measured. Results: In diabetic rats, NaSH only at doses of 0.56 and 1.6 mg/kg increased recovery of LVDP (16% and 42%), +dp/dt (25% and 35%) and –dp/dt (23% and 32%) as well as decreased infarct size (44% and 35%). At these doses, NaSH increased expressions of cystathionine γ-lyase (CSE) (440% and 271%) and endothelial NO synthase (eNOS) (232% and 148%) but it decreased the expressions of inducible NOS (iNOS) (55% and 71%). NaSH at 0.28, 2.8 and 5.6 mg/kg had no significant effects on these parameters. Conclusion: NaSH had a bell-shaped cardioprotective effect against myocardial IR injury in rats with T2D. Higher tolerance to IR injury in heart isolated from type 2 diabetic rats treated with intermediate doses of NaSH is associated with higher CSE-derived H<sub>2</sub>S and eNOS-derived NO as well as lower iNOS-derived NO.</p>}},
author = {{Jeddi, Sajad and Gheibi, Sevda and Kashfi, Khosrow and Carlström, Mattias and Ghasemi, Asghar}},
issn = {{0024-3205}},
keywords = {{HS-producing enzymes; Hydrogen sulfide; Infarct size; Ischemia-reperfusion injury; NO-producing enzymes; Type 2 diabetes}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Life Sciences}},
title = {{Protective effect of intermediate doses of hydrogen sulfide against myocardial ischemia-reperfusion injury in obese type 2 diabetic rats}},
url = {{http://dx.doi.org/10.1016/j.lfs.2020.117855}},
doi = {{10.1016/j.lfs.2020.117855}},
volume = {{256}},
year = {{2020}},
}