Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazolebased compounds in experimental animals
Purpose: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of
disorders, their administration is associated with gastrointestinal side effects, acute kidney injury
and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents
with better safety profile. The aim of the current study was to evaluate the chronic efficacy and
safety profile of two compounds previously proven to have acceptable acute anti-inflammatory
and analgesic activities.
Materials and methods: Doses were determined through formalin-induced mice paw edemabased
dose–response curves. Granuloma weight was used to assess the chronic effect of the
investigated compounds as compared to the vehicle and diclofenac representing the positive
and the negative controls, respectively. Mice kidneys, livers and stomachs were histologically
examined. Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum
creatinine and blood urea nitrogen levels were measured.
Results: The results highlight that the granulomas and exudates developed in mice after 7 days
of treatment, with compound I and compound II were significantly lower than that of the negative
control group. Moreover, compound I showed significantly better anti-inflammatory effect than
diclofenac. Troponin level was undetected in all groups. Histopathological examination of the
stomach revealed normal mucosa for both tested compounds and controls. Likewise, kidneys
showed neither significant histologic alteration nor biomarkers increase as compared to the
control over both 7- and 30-day treatment periods. Mice that received the tested compounds or
diclofenac exhibited transient liver damage specifically; congestion, vacuolization, necrosis and
inflammation after 7 days of treatment which decreased significantly after 30 days of treatment
as emphasized by the Suzuki score and biomarker levels.
Conclusion: Since the tested compounds, specifically compound I, presented a satisfactory
chronic safety profile as well as anti-inflammatory effect, it is worth conducting further molecular
pharmacological, toxicological and bioavailability studies to elucidate the efficacy of these
potential anti-inflammatory bipyrazole compounds.
Keywords: peptic ulcer, hepatic injury, kidney injury, nonsteroidal anti-inflammatory drugs,
Hanan Ragab, Hania Nakkash Chmaisse, Ahmed El Mallah, Mohammad Mehanna
Journal of Inflammation Research,DOI: https://doi.org/10.2147/JIR.S157955, ISSN: 1178-7031, Volume: 11, Issue: 0, Pages Range: 143-153