Background: Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of several human cancers, but its usefulness is limited by its hepatotoxicity which sometimes requires discontinuation of the treatment. A number of drugs were used to ameliorate the injurious effect of cisplatin on liver. One of the most important of these drugs is L-carnitine.
Aim of the work: The present study was designed to investigate the different pathological effects and the extent of apoptosis induced by cisplatin in liver tissue, and the potential protective effect of L-carnitine against it. This in turn, may affect the treatment regime of cisplatin.
Material and methods: Eighty adult male Wistar albino rats were divided into 5 groups. Group I (control group) contained 20 rats, whereas each of the other groups contained 15 rats. These experimental groups were cisplatin group (group II) which received saline injection 5 days prior and after a single cisplatin injection (7 mg/kg IP), cisplatin recovery group (group III) which received saline 5 days before and 21 days after a single cisplatin injection of the same dose. Cisplatin and L-carnitine group (group IV) and cisplatin and L-carnitine recovery group (group V) corresponded to groups II and III respectively in their time design, but L-carnitine was used instead of saline. Liver specimens were subjected to hematoxylin and eosin, Masson trichrome, silver staining as well as immunohistochemical Caspase-3 examination and measurements utilizing image analysis technique.
Results: The histological results revealed the injurious effect of cisplatin on the liver. The groups treated with cisplatin alone showed degeneration featured by cytoplasmic vacuolization, ghost figures, karyolysis, pyknosis, mononuclear cellular infiltration, hypochromatic nuclei, multiple nucleoli, intranuclear vacuolization, portal congestion and oedema and necrotic cells. The lesions affected mainly the pericentral and midzonal areas. The groups treated with cisplatin and L-carnitine showed mild or no affection, with preservation of normal hepatic architecture. The central vein diameter, the stromal framework disruption and apoptotic cells increased in the cisplatin groups, but it was much less affected in the cisplatin and L-carnitine groups. The recovery groups showed statistically higher values as regards the area percent of fibrous tissue, with partial privilege to the L-carnitine combined treatment
Conclusion: The present work revealed that L-carnitine provided an excellent protective factor against the damaging effects of cisplatin on the liver as regards general histological picture, stromal framework integrity, central vein diameter and apoptosis, but it partially protected the liver against fibrosis. The safeguarding effect of L-carnitine increased with its administration for a longer period before and after cisplatin.