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Crocetin ameliorative effect on diabetic nephropathy in rats through a decrease in transforming growth factor-β and
Mohammad Mazani1, Sina Mahdavifard2, Alireza Koohi3
1Professor of the Department of Clinical Biochemistry, Ardabil University of Medical Sciences, Ardabil, Iran.
Background & Aims:
Glycation, oxidative stress, and inflammation due to the elevation of transforming growth factor-β1 (TGF-β1) participate in diabetic nephropathy (DN). Thus, we investigated for the first time the effect of crocetin (Crt) on the renal histopathological parameters, TGF-β1 and glycation, oxidative stress, as well as inflammatory markers in the DN rat model.
Methods:
Forty male Wistar rats were randomly divided into 4 equal groups: normal (N), N + Crt, DN, and DN + Crt. DN was induced in rats with a combination of nephrectomy and streptozotocin. Treated groups received 100 mg/kg of Crt via intraperitoneal injection monthly for 3 months. Different glycation (glycated albumin, glycated LDL, Methylglyoxal, and pentosidine), oxidative stress (advanced oxidation protein products, malondialdehyde, glutathione, and paraoxonase-I (PON-1)), and inflammatory markers (tumor necrosis factor-α, myeloperoxidase, and TGF-β1), blood glucose, insulin, lipid profile, creatinine in the serum, and proteinuria, as well as the glyoxalase-1 (GLO-1) activity, was determined.
Results:
Crt decreased renal biochemical (Cre and PU) and histopathological (glomerulosclerosis) renal dysfunction parameters, diverse glycation, oxidative stress, and inflammatory markers in the DN rats. Furthermore, the treatment corrected glycemia, insulin resistance, and dyslipidemia as well as induced the activities of GLO-1 and PON-1. Over and above, the treatment decreased TGF-β1 in their serum (p > 0.001).
Conclusions:
Crocetin improved DN owing to an advantageous effect on metabolic profile. Further, the treatment with a reducing effect on TGF-β1, oxidative stress, glycation, and inflammation markers along with an increase in Glo-1 activity showed multiple protective effects on kidney tissue.
Insights
Crocetin (Crt) treatment improved diabetic nephropathy (DN) in rats by reducing glycation, oxidative stress, and inflammation. This natural compound also improved metabolic profiles and protected kidney tissue.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Diabetic nephropathy (DN) involves glycation, oxidative stress, and inflammation, often linked to elevated transforming growth factor-β1 (TGF-β1).
- Investigating novel therapeutic agents is crucial for managing DN progression and its associated complications.
Purpose of the Study:
- To evaluate the therapeutic effects of crocetin (Crt) on renal histopathology, TGF-β1, and markers of glycation, oxidative stress, and inflammation in a rat model of DN.
- To determine Crt's impact on metabolic parameters including glycemia, insulin resistance, and lipid profiles in DN rats.
Main Methods:
- Diabetic nephropathy was induced in male Wistar rats using a combination of nephrectomy and streptozotocin.
- Rats were divided into normal, normal + Crt, DN, and DN + Crt groups, with Crt administered intraperitoneally (100 mg/kg) monthly for 3 months.
- Assessed parameters included renal function markers, various glycation and oxidative stress markers, inflammatory cytokines, and TGF-β1 levels.
Main Results:
- Crocetin treatment significantly reduced biochemical and histopathological markers of renal dysfunction, including glomerulosclerosis.
- Crt administration ameliorated diverse glycation, oxidative stress, and inflammatory markers while improving glycemia, insulin resistance, and dyslipidemia.
- The treatment increased the activity of glyoxalase-1 (GLO-1) and paraoxonase-I (PON-1) and decreased serum TGF-β1 levels.
Conclusions:
- Crocetin demonstrates significant protective effects against diabetic nephropathy in rats, primarily through an improved metabolic profile.
- The compound's ability to reduce TGF-β1, oxidative stress, glycation, and inflammation, coupled with enhanced GLO-1 activity, highlights its multi-faceted renoprotective potential.
