Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors

Abstract

Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg·day) or NTZ (200 mg·kg·day) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

Aerobic exercise decreases chemerin/CMKLR1 in the serum and peripheral metabolic organs of obesity and diabetes rats by increasing PPARγ

“…Similar results were reported by other researchers, who reported that the FINS in HFD-STZ induced diabetes rats was still increased by about 2-fold at 4 weeks after 35 mg/kg of STZ injection [39] and at 12 weeks after 45 mg/kg of STZ injection [40]. Elaidy et al reported that the FINS in HFD-STZ (50 mg/kg) induced diabetes rats was time-dependent, reflected by higher level at the third week after STZ injection while reductions from the forth week post-injection till the end of the study [41]. So we speculated that the high level of FINS in our diabetes rats was likely to be attributed to lower dosage of STZ (30 mg/kg body weight) and short time after STZ injection (4 weeks).…”

The Antidiabetic and Antinephritic Activities of Auricularia cornea (An Albino Mutant Strain) via Modulation of Oxidative Stress in the db/db Mice

“…Insufficient insulin leads to the accumulation of lipids, specifically TG and TC, in hyperglycemic patients, and thus causes diabetes-related complications (42). The accumulation of excessive adipose cells in the liver leads to hepatic steatosis and further fatty liver damage (43). The beneficial effects of AU on lipid metabolism indices and liver structures strongly confirmed its protective effect on the liver in the db/db mice.…”

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

“…We now explain the pathways of SARS-CoV-2 entry and pathogenesis, systematically juxtaposing at each stage the role of nitazoxanide elucidating thereby the ability of the drug to exhibit direct antiviral action and host beneficial anti-inflammatory response to curb the cytokine storm. Importantly nitazoxanide is also reported to be useful in patients with co-morbidities ( Elaidy et al, 2018 ; Fan et al, 2019 ; Ghusson and Vasquez, 2018 ; Nitazoxanide in fibrosis, 2020).…”