Protective effect of crocin on liver toxicity induced by morphine

Abstract

Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters.

Keywords: Crocin; Liver toxicity; Mice; Morphine.

Fig. 1

Effects of crocin, morphine and crocin plus morphine on the liver weight of various groups of Balb/c male mice. *Significant increase in crocin+morphine group (12.5 mg/kg) compared to morphine group (P<0.05). **Significant increase in crocin+morphine group (25 mg/kg) compared to morphine group (P<0.05). ***Significant increase in crocin+morphine group (50 mg/kg) compared to morphine group (P<0.05)

Fig. 2

Effects of crocin, morphine and crocin plus morphine on the mean hepatocytes diameter various groups of Balb/c male mice. *Significant decrease in crocin+morphine group (12.5 mg/kg) compared to morphine group (P<0.05). **Significant decrease in crocin+morphine group (25 mg/kg) compared to morphine group (P<0.05). ***Significant decrease in crocin+morphine group (50 mg/kg) compared to morphine group (P<0.05).

Fig. 3

Effects of crocin, morphine and crocin plus morphine on the mean central hepatic vein diameter of various groups of Balb/c male mice. *Significant decrease of the mean central hepatic vein diameter in crocin+morphine group (12.5 mg/kg) compared to morphine group (P<0.05). **Significant decrease in crocin+morphine group (25 mg/kg) compared to morphine group (P<0.05). ***Significant decrease in crocin+morphine group (50 mg/kg) compared to morphine group (P<0.05).

Fig. 4

Histological changes of liver hematoxylin-eosin staining (magnification 100×). A; Micrograph of liver section of mice in saline group showing a normal liver structure. B; Micrograph of liver section treated with crocin (50 mg/kg) showing a normal liver structure. C; Micrograph of liver section treated with morphine showing more distributed Kupffer cells around central vein (thin arrow) and enlargement of central hepatic vein (thick arrow). D; Micrograph of liver section treated with crocin plus morphine showing normal liver structure.

Fig. 5

Effects of crocin, morphine and crocin plus morphine on the mean nitric oxide levels of various groups of Balb/c male mice. *Significant decrease of nitric oxide in group of crocin+morphine group (12.5 mg/kg) compared to morphine group (P<0.05). **Significant decrease in crocin+morphine group (25 mg/kg) compared to morphine group (P<0.05). ***Significant decrease in crocin+morphine group (50 mg/kg) administration compared to morphine group (P<0.05).

Fig. 6

Effect of morphine, crocin and crocin plus morphine administration on liver enzymes of various groups of Balb/c male mice. A; AST enzyme, B; ALT enzyme and C; ALD enzyme. *Significant decrease in crocin+morphine group (12.5 mg/kg) compared to morphine groups (P<0.05). **Significant decrease in crocin+morphine group (25 mg/kg) compared to morphine groups (P<0.05). ***Significant decrease in crocin+morphine group (50 mg/kg) administration compared to morphine groups (P<0.05)