Related Experiment Video
Updated: Jun 10, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Saroglitazar ameliorates 5- Fluorouracil-induced hepatorenal damage in rats
Alhomedy M Alharbi1, Hoda E Kafl1, Rania R Abdelaziz1
1Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Rationale:
Hepatotoxicity and nephrotoxicity are significant adverse effects caused in cancer patients treated with 5-Flurouracil (5-FU), a pyrimidine analogue anti-metabolite anticancer drug. The purpose of this research was to evaluate the impact of PPAR α/γ agonist (Saroglitazar; SARO) on 5-FU-induced hepatorenal damage in rats.
Methods:
Male rats were randomly assigned to four groups: control, 5-FU, 5-FU + SARO (2 mg/kg), and 5-FU + SARO (4 mg/kg). Rats received 75 mg/kg 5-FU intraperitoneally once weekly for three weeks. Saroglitazar (2 and 4 mg/kg/day) was orally supplied by oral syringe for three consecutive weeks. On day 22, rats were euthanized and their livers and kidneys were subjected to morphological, biochemical, histological, and immunohistochemical analysis.
Results:
Saroglitazar treatment significantly decreased serum liver and kidney function biomarkers. In addition, it successfully modulated liver and kidney levels of inflammatory mediators and markers (NF-κB P65, TNF-α, cleaved caspase-1, IL-1β and p-p38 MAPK) and oxidative stress-related parameters (MDA, GSH, SOD, Keap1, Nrf-2 and HO-1) in a dose dependent manner. Furthermore, SARO could attenuate 5-FU-induced activation of cleaved caspase-3 as well as improved histopathological examination of both liver and kidney tissues.
Significance:
Saroglitazar may be a viable therapy option for 5-FU toxicity as it halts the interaction network of NF-kB and Nrf2 signaling pathways and apoptosis.
Insights
Saroglitazar (SARO) mitigated liver and kidney damage caused by 5-Flurouracil (5-FU) chemotherapy in rats. This PPAR agonist protected against 5-FU toxicity by reducing inflammation and oxidative stress.
Area of Science:
- Pharmacology
- Toxicology
- Oncology
Background:
- 5-Flurouracil (5-FU) chemotherapy causes significant hepatotoxicity and nephrotoxicity in cancer patients.
- Understanding and mitigating these adverse effects is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the protective effects of Saroglitazar (SARO), a PPAR α/γ agonist, against 5-FU-induced liver and kidney damage in a rat model.
- To investigate the underlying mechanisms of Saroglitazar's protective action.
Main Methods:
- Male rats were administered 5-FU weekly for three weeks.
- Saroglitazar (2 and 4 mg/kg) was administered orally daily for three weeks.
- Liver and kidney tissues were analyzed using morphological, biochemical, histological, and immunohistochemical methods.
Main Results:
- Saroglitazar significantly reduced serum liver and kidney function biomarkers.
- It dose-dependently modulated inflammatory markers (NF-κB, TNF-α, caspase-1, IL-1β, p38 MAPK) and oxidative stress parameters (MDA, GSH, SOD, Keap1, Nrf-2, HO-1).
- Saroglitazar attenuated 5-FU-induced apoptosis (caspase-3 activation) and improved tissue histopathology.
Conclusions:
- Saroglitazar demonstrates potential as a therapeutic option to manage 5-FU-induced hepatorenal toxicity.
- Its protective effects are linked to the modulation of NF-kB and Nrf2 signaling pathways and apoptosis.
More Related Videos
Related Concept Videos
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...