This study evaluated the effects of GIT-27 on methotrexate-induced liver injury in rats. The study aimed to determine if GIT-27, an anti-inflammatory immunomodulating agent, could reverse changes caused by methotrexate or have hepatoprotective potential. Rats were divided into four groups: a control group, a vehicle pre-treated group, a methotrexate group, and a GIT-27 pre-treated group. Various biomarkers and histopathological analysis were used to measure liver injury. The results showed that methotrexate caused significant increases in biomarkers of liver injury and inflammation as well as severe liver damage. However, rats pretreated with GIT-27 showed alleviated biomark

1. Evaluation of the effects of GIT-27 on methotrexate-induced liver injury
Bassim I. Mohammad University of Al-Qadisiyah/College of Pharmacy
Bassim S. Ahmed Al-Mustansiriyah University/ College of Medicine
Alaa F. Hassan Al-Mahmoudiya General Hospital
Introduction:Methotrexate-induced liver injury is a common problem that is described either an increased
level of hepatic biomarkers, or as idiosyncratic induced liver injury or as fibrosis and cirrhosis. This profile
may rarely progress to acute liver failure.
The aim of the study: To investigate whether treating the animals with GIT-27 would reverse the changes
induced by methotrexate, or whether GIT-27 has a valuable hepatoprotective potential, especially
considering that it is an anti-inflammatory immunomodulating agent.
Methods:
Experimental Design: This study included 28 male albino-wistar rats (aged 4-6 months) (weight 125-225
g). The animals were divided into random 4 groups: Control group: Rats were kept on a regular diet and
distilled water throughout the 14 experimental days. Vehicle pre-treated group:Rats were administered
i.p. dimethyl sulfoxide for 7 days followed by 7 days of oral methotrexate 0.2mg/kg/day. Methotrexate
group: Ratswere left untreated for 7 days followed by 7 days of oral methotrexate 0.2mg/kg/day (Olayinka
E. et al., 2016). GIT-27 pre-treated group: Rats were administered 4 i.p. challenge doses of GIT-27
25mg/kg at 168, 120, 72 and 24 hours before starting treatment with oral methotrexate 0.2mg/kg/day for 7
days (Hadi N. & Jabber H., 2016; Olyinka E. et al., 2016).
Parameters measured in this study: serum level of alanine aminotransferase,aspartate
aminotransferase, alkaline phosphatase, interleukin-6, and tumour necrosis factor‑α,level of lipid
peroxide, malondialdehyde, reduced glutathione, hepatobiliary bilirubin and total serum protein.
Histopathological study: It was done according to the steps of the paraffin-embedded method (Suvarna
S., Layton C., and Bancroft J., 2013). Liver structure evaluation was done utilizing the histological
scoring system for the nonalcoholic fatty liver disease after Kleiner D. et al., (2005)
Results: the significant increase in biomarkers of hepatic function, inflammatory and oxidative stress
biomarkers, as well as severe liver histopathologic change “steatosis” seen in animals treated with
methotrexate, were alleviated in animals pretreated with GIT-27. With significant improvement in serum
level of aspartate aminotransferase, alkaline phosphatase, interleukin-6, tumour necrosis factor-α,
malondialdehyde and reduced glutathione, besides an improved histopathologic profile of moderate
steatosis.
Conclusion: This study suggests that GIT-27 protect against liver injury induced by methotrexate
depending on their antagonism of the inflammatory Toll-like receptors-4 and -2/6.