Dexamethasone increases renal free fatty acids and xanthine oxidase activity in female rats: could there be any gestational impact?

Free fatty acids deposition in non-adipose tissues such as the heart is a characteristic of insulin resistant states which features hyperinsulinemia and dipeptidyl peptidase-4 (DPP-4) activation. Estrogen-progestin oral contraceptives (OC) treatment reportedly increased DPP-4 activity in rat tissue and DPP-4 inhibitors have anti-diabetic and anti-inflammatory properties. This study aims to investigate the effects of DPP-4 inhibition on cardiac free fatty acid (FFA) deposition in estrogen-progestin treated female rats.From our data, estrogen-progestin OC exposure in female rats led to elevated plasma insulin, cardiac DPP-4 activity, FFA and triglyceride (TG) accumulation, Triglyceride/high density lipoprotein (TG/HDL) ratio, adenosine deaminase/xanthine oxidase/uric acid pathway, lipid peroxidation, glycogen synthase activity and alanine phosphatase whereas cardiac glucose-6-phosphate dehydrogenase, Na/K-ATPase and nitric oxide (NO) were decreased. However, DPP-4 inhibition resulted in decreased plasma insulin, cardiac DPP-4 activity, FFA, TG and TG/HDL-C ratio and alkaline phosphatase. These were accompanied by reduced adenosine deaminase/xanthine oxidase/uric acid (ADA/XO/UA) pathway, lipid peroxidation and augmented NO and Na/K-ATPase in estrogen-progestin OC-treated rats.DPP-4 inhibition attenuated cardiac lipid deposition accompanied by reduced activity in the ADA/XO/UA pathway in estrogen-progestin OC-treated female rats. DPP-4 is therefore a plausible therapeutic target in cardiometabolic disorders

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Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females

Life ◽

10.3390/life12010016 ◽

2021 ◽

Vol 12 (1) ◽

pp. 16

Author(s):

Nikola Tatalović ◽

Teodora Vidonja Uzelac ◽

Milica Mijović ◽

Gordana Koželj ◽

Aleksandra Nikolić-Kokić ◽

...

Keyword(s):

Xanthine Oxidase ◽

Oxidase Activity ◽

Antioxidant Activities ◽

Specific Effect ◽

Female Rats ◽

Male Rats ◽

Central Vein ◽

Xanthine Oxidase Activity ◽

Rapid Changes ◽

Cellular Energetics

Ibogaine induces rapid changes in cellular energetics followed by the elevation of antioxidant activities. As shown earlier in male rats, ibogaine treatment with both 1 and 20 mg/kg b.w. per os led to significant glycogenolytic activity in the liver. In this work, female rats treated with the same doses of ibogaine per os displayed lower liver glycogenolytic activity relative to males, dilatation of the central vein and branches of the portal vein, and increased concentration of thiols 6 h after treatment. These changes were followed by increased catalase activity and lipid peroxidation, and decreased xanthine oxidase activity after 24 h. In kidneys, mild histopathological changes were found in all treated animals, accompanied by a decrease of glutathione reductase (after 6 and 24 h at both doses) and an increase of catalase (6 h) and xanthine oxidase activity (6 and 24 h). Ibogaine did not affect antioxidant enzymes activity in erythrocytes. Bioavailability of ibogaine was two to three times higher in females than males, with similar kinetic profiles. Compared to previous results in males, ibogaine showed sex specific effect at the level of antioxidant cellular system. Effects of ibogaine in rats are sex- and tissue-specific, and also dose- and time-dependent.

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