In Vivo Toxicity of Solasonine and Its Effects on cyp450 Family Gene Expression in the Livers of Male Mice from Four Strains

Abstract

Solasonine was reported to inhibit tumour cell growth in several different models. The in vivo toxicity of solasonine, the effects of genetic background on its toxicity, and its possible roles in regulating the expression of cyp450 family genes were still unclear and required characterisation. Here, Horn’s assays were performed on male mice from four different strains, and the expression of cyp450 family genes in their livers was examined by RT-PCR and ELISA. Mice treated by intraperitoneal injection with high levels of solasonine showed immediate post-excitatory depression, intraperitoneal tissue adhesion, and dissolving of cells in the liver. Furthermore, these four mouse strains showed different toxicological sensitivity to solasonine. The strains, in decreasing order of LD50 value, rescuing speed of body weight, and more severe pathological symptoms, were KM, ICR, C57BL/6, and BALB/c. Interestingly, more cyp450 genes were downregulated at the mRNA and/or protein level in the livers of male mice from C57BL/6 or BALB/c strains than those from KM or ICR strains. These results suggest that (1) Solasonine has hepatic toxicity and downregulates cyp450 genes expression at transcriptional and/or post-transcriptional levels; (2) Genetic background is an important factor which can affect the in vivo toxicity; (3) Downregulation of cyp450 gene expression in the liver may be a clue to help understand whether or not a given strain is sensitive to solasonine; (4) Influences on the expression of cyp450 genes should be considered when using solasonine alone, or in combination with other drugs.

Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors

“…We also found that protein and mRNA levels of CHST4 were low in the liver in BALB/c mice, while high mRNA levels and low protein levels were observed in the pancreas. In contrast, the mRNA levels of CHST4 were high in the pancreas and liver in C57BL/6 mice (12), which may be related to the different strains of mice (45). The difference in protein and mRNA levels may be due to translation or posttranslational modifications (46) of CHST4, although this has not yet been verified.…”

Solanum nigrum Fruit Extract Increases Toxicity of Fenitrothion—A Synthetic Insecticide, in the Mealworm Beetle Tenebrio molitor Larvae

“…The extract possesses medicinal properties [ 14 ] including anticancerous ones [ 15 ]. Solasonine and solamargine also have anticancer properties proved in many studies [ 16 , 17 , 18 ], having low toxicity [ 19 , 20 ]. Additionally, the persistence in the environment of glycoalkaloids is short [ 21 ].…”

Diuretic activity and mechanism of Mosla chinensis Maxim. cv. Jiangxiangru in normal Rats

“…Primer sequences and PCR ampli cation reactions were as according to the literature (Yan, Zeng et al 2014). The internal reference gene of the experiment was GAPDH (Zhong, Li et al 2018). The primer sequences and reaction systems are shown in Tables 1 and 2.…”