Umbelliferone ameliorates oxidative stress and testicular injury, improves steroidogenesis and upregulates peroxisome proliferator-activated receptor gamma in type 2 diabetic rats

Autor: Samah Elattar, Mohamed A M Allam, Akef A Khowailed, Ayman M. Mahmoud
Rok vydání: 2020
Předmět:
Male
endocrine system
medicine.medical_specialty
Pharmaceutical Science
Peroxisome proliferator-activated receptor
Inflammation
medicine.disease_cause
Antioxidants
Diabetes Mellitus
Experimental
Lipid peroxidation
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Insulin resistance
Internal medicine
Diabetes mellitus
Testis
medicine
Animals
Testosterone
Umbelliferones
030304 developmental biology
Pharmacology
chemistry.chemical_classification
0303 health sciences
business.industry
Hydroxysteroid Dehydrogenases
medicine.disease
Streptozotocin
Rats
PPAR gamma
Oxidative Stress
Endocrinology
chemistry
Diabetes Mellitus
Type 2
030220 oncology & carcinogenesis
Hyperglycemia
Cytokines
medicine.symptom
business
Pioglitazone
Oxidative stress
Gonadotropins
medicine.drug
Zdroj: The Journal of pharmacy and pharmacology. 74(4)
ISSN: 2042-7158
Popis: Objectives Diabetes mellitus (DM) is a chronic disease associated with serious complications, including male infertility. Umbelliferone (UMB) is a coumarin with promising antioxidant, anti-inflammatory and other beneficial effects. This study investigated the ameliorative effect of UMB against testicular injury, oxidative stress and altered steroidogenesis in rats with type 2 DM. Methods Rats received a high fat diet for 4 weeks followed by a single injection of streptozotocin. Diabetic rats were treated with UMB or pioglitazone (PIO) for 6 weeks and samples were collected for analysis. Key findings Diabetic rats exhibited hyperglycemia, insulin resistance and dyslipidemia associated with increased serum pro-inflammatory cytokines, and decreased gonadotropins and testosterone. UMB significantly ameliorated metabolic alterations, decreased pro-inflammatory cytokines, and increased gonadotropins and testosterone levels. UMB prevented testicular injury, suppressed lipid peroxidation and nitric oxide and increased antioxidants in diabetic rats. In addition, UMB upregulated testicular gonadotropins receptors, steroidogenesis markers (steroidogenic acute regulatory protein, cytochrome P450 family 17 subfamily A member 1 [CYP17A1], 3β-hydroxysteroid dehydrogenase [3ß-HSD] and 17ß-hydroxysteroid dehydrogenase [17ß-HSD]), and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Conclusions UMB prevents testicular injury by preventing metabolic alterations, suppressing oxidative damage and inflammation, and boosting antioxidant defenses in diabetic rats. UMB enhanced pituitary-gonadal axis and steroidogenesis and upregulated testicular PPARγ in diabetic rats. Thus, UMB may represent a protective agent against testicular injury and sexual dysfunction associated with chronic hyperglycemia.
Databáze: OpenAIRE
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