Abstract
Cisplatin (CP) is one of the most active medications in cancer treatment and has some adverse effects such as hepatotoxicity and nephrotoxicity. The present research was planned to determine the protective effects of L-carnitine (LC) against CP-induced hepato-renal oxidative stress in rats, via investigating of some serum biochemical and tissue oxidative/antioxidant parameters, histological alterations, and immunohistochemical expressions of two different intermediate filaments (IFs) proteins; vimentin (VIM) and cytokeratin 18 (CK18). Twenty-eight rats were divided into four groups (7 rats each). Groups I and II were orally administered saline and LC (100 mg/kg body weight), respectively, once daily for 30 consecutive days. Group III received saline orally once daily and a single dose of CP on the 27th day of the experiment [7.5 mg/kg, intraperitoneal (IP)]. Group IV received both LC and CP. Injection of CP significantly (P ≤ 0.05) increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities and creatinine and urea levels, while serum total protein, albumin, and globulin concentrations significantly (P ≤ 0.05) decreased. In addition, CP induced a dramatic increase in the Malondialdehyde (MDA) level along with a substantial decrease in reduced glutathione (GSH) and catalase (CAT) in the hepato-renal tissues. Histologically, both liver and kidney of the CP treated group revealed marked degenerative changes. Moreover, overexpression of both VIM and CK18 in hepato-renal tissues were noted after CP injection. On the other hand, the administration of LC in the CP injected group (Group IV) restored the biochemical parameters, histological, and immunohistochemical pictures toward the normalcy. In conclusion, LC may be supplemented for chemotherapy with CP to ameliorate its oxidative stress and restore the normal organization of IFs, especially VIM and CK18 within the CP intoxicated hepato-renal cells.
Highlights
Under normal conditions, the various cell types of both liver and kidney have characteristic cytoskeleton and intermediate filaments (IFs) compositions, which are involved in the cell shape maintenance, mechanical stability, and intracellular organization and transport (Ku et al, 1999)
CKs are known as cellular stress protein, specially cytokeratin 18 (CK18), which use as novel markers of the liver and kidney injuries (Yang et al, 2015; Djudjaj et al, 2016)
LC+CP administrated group revealed a decrease in MDA level along with elevations in GSH and CAT in hepatic and renal tissues compared with CP treated group (Table 2)
Summary
The various cell types of both liver and kidney have characteristic cytoskeleton and intermediate filaments (IFs) compositions, which are involved in the cell shape maintenance, mechanical stability, and intracellular organization and transport (Ku et al, 1999). Vimentin (VIM) is the IF of the non-epithelial cells, especially those of mesenchymal origin (Sen et al, 2010). Cytokeratins (CKs) represent the largest and most common epithelial IFs (Snider, 2016). Inflammation, apoptosis, and oxidative stress were mentioned as the most relevant pathways for CP toxicity (Meng et al, 2017) as well as, disorganization of the IFs components of the cytoskeleton (Evans and Simpkins, 1998). VIM is considered a mesenchymal marker for liver and kidney toxicity (Matos et al, 2007; Wang et al, 2017). CKs are known as cellular stress protein, specially CK18, which use as novel markers of the liver and kidney injuries (Yang et al, 2015; Djudjaj et al, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
