Page 46 - Pharma News Letter Vol1 Issue2 - Converted By Dr. Ahmed Rashed

Chapter VI

International Immunopharmacology

Volume 115, February 2023, 109688

Saroglitazar, a dual PPAR-α/γ agonist, alleviates LPS-induced
hepatic and renal injury in rats

Marina R. Francis1, Ahmed R. El-Sheakh ,
1
Ghada M. Suddek1
1 Department of Pharmacology and Toxicology,
Faculty of Pharmacy, Mansoura University,
Mansoura, Egypt.
Abstract

Background: Lipopolysaccharide (LPS), an
endotoxin within gram-negative bacteria, is
associated with systemic acute inflammatory
response after invading living tissues and results
in sepsis. The liver and kidney are both major
target organs in sepsis. Septic acute hepatic-renal
injury is a serious clinical condition with high
risk of morbidity and mortality. Nevertheless,
effective treatment is still lacking.

Aim: This study highlights saroglitazar (SAR),
a dual PPAR-α/γ agonist, as a proposed activation of non-canonical inflammasome
prophylactic drug against LPS-induced hepatic-
renal injury. and pyroptosis via a significant reduction
in cysteinyl aspartate-specific proteinase-11
Main methods: Rats were pretreated with SAR (Caspase-11) and gasdermin D (GSDMD)
(2 and 4 mg/kg/day) for 15 days, while sepsis expressions. Moreover, Nucleotide-Binding
was induced by LPS injection (10 mg/kg) on day Oligomerization Domain (NOD)-Like Receptor
15 one hour following SAR oral administration. Protein 3 (NLRP3) inflammasome activation

Key findings: SAR pretreatment could with concomitant expression and activation of
successfully mitigate LPS-induced hepatic- caspase-1 and release of interleukin-1beta (IL-
renal injury, evidenced by enhancement of 1β) were considerably diminished following
renal and hepatic functions and a decrease of SAR pretreatment.
tissue pathological injury. Meanwhile, SAR Significance: SAR could be considered a
alleviated LPS-induced oxidative stress; it prophylactic anti-inflammatory antioxidant
reduced malondialdehyde (MDA) levels and drug against LPS-induced liver and kidney
ameliorated decreased levels of superoxide injury.
dismutase (SOD) and glutathione (GSH). LPS-
induced elevations in hepatic and renal nuclear https://doi.org/10.1016/j.intimp.2023.109688
factor-kappa B (NF-κB), phosphorylated
inhibitor of kappa B alpha (p-IκBα), interferon-
beta (IFN-β), and hepatic high mobility group
box-1 (HMGB-1) contents were significantly
attenuated in SAR-treated groups. SAR showed
an advantageous impact against LPS-induced

46 Faculty of Pharmacy Newsletter