Histopathological and biochemical assessment of liver damage in albino Wistar rats treated with cytotoxic platinum compounds in combination with 5-fluorouracil

Abstract

Introduction: Chemotherapy-induced hepatotoxicity in cancer patients often results in cessation of therapy and prevents completion of the treatment plan. The entire pathological description and comparison of hepatic damage induced by oxaliplatin or cisplatin in combination with 5-fluorouracil (5-FU) is not adequately reported. This study reports histopathological assessment of hepatotoxicity of a non-tumor bearing organ in rats treated with 5-FU, oxaliplatin and cisplatin (CDDP). Material and methods: Changes in hepatic biochemical profile of 36 albino Wistar rats equally divided into different treatment groups with cisplatin, oxaliplatin, 5-FU, cisplatin plus 5-FU and oxaliplatin plus 5-FU were compared with a group of rats treated with normal saline (control group). At the end of treatments, hepatic tissues were taken for blinded histopathological assessment by light microscopy. Results: Serum glutamate pyruvate transaminase and serum glutamic-oxaloacetic transaminase levels were disrupted in rats treated with 5-FU alone and in combination with cisplatin or oxaliplatin. Hepatocellular injuries, e.g. sinusoidal dilatation, venular fibrosis and centrilobular vein injury induced by oxaliplatin were intensified in treatment groups also receiving 5-FU, manifested as massive architectural distortion, periportal fibrosis, hepatic cord degeneration and cystic lesions with demarcated margins. Hepatocellular degenerative sequence and abnormally dilated central hepatic vein was shown in the cisplatin plus 5-FU treatment group with hemorrhage and blood filled sinusoids. Conclusions: Oxaliplatin-associated cystic lesions were intensified in rats treated with a combination of 5-FU and oxaliplatin.

Methanolic Phoenix dactylifera L. Extract Ameliorates Cisplatin-Induced Hepatic Injury in Male Rats

“…These results are in agreement with Palipoch and Punsawad [ 57 ]. Several studies have identified the hepatotoxic effect of Cis [ 58 , 59 , 60 ].…”

Hepatoprotective Potential of Lycopene in a Rat Model of Cisplatin-Induced Damage: Involvement of Oxidative Cell Damage and Glutathione Metabolism

“…Histopathological findings usually collaborate with the results of biochemical and tissue parameters of CP toxicity [52] and in the present study, microvacuolar degeneration and hepatic necrosis are in accordance with the CP hepatotoxic potential (Table 2 and fig. 3C) [53] . On the other hand, in the group treated with CP and LYC, rare microvacuolar degeneration were still present, however to a much lesser extent (Table 2 and fig.…”

All-trans Retinoic Acid combined with oxaliplatin suppressed proliferation of chemo-resistant hepatocellular carcinoma cells by inducing G2/M cell cycle arrest

“…Several clinical trials have shown that OXA represents a viable and reasonable chemotherapeutic option in advanced HCC [19][20][21]; however, high drug resistance and side effect rates greatly limit clinical application of chemotherapy. Therefore, addressing chemotherapy resistance is very urgent and important.…”

“…Therefore, addressing chemotherapy resistance is very urgent and important. Several studies have explored the efficacy of OXA in combination with other drugs, such as sorafenib, ramucirumab, and ADI-PEG 20 [12][13][14][15][16][17][18][19][20][21][22][23][24]. However, the results of these clinical studies were unsatisfactory, and there are no in-depth studies of the molecular mechanisms.…”