Rosa roxburghii Tratt juice can improve S-adenosylmethionine consumption and liver damage induced by arsenic in rats

Background Arsenic exposure can lead to liver dysfunction, liver steatosis, hepatitis, liver fibrosis, and other liver injuries, but its mechanism is still unclear and effective treatment methods are lacking.

Objective To investigate the potential intervention effect and associated mechanism of Rosa roxburghii Tratt juice on arsenic-induced liver injury in rats from the perspective of S-adenosylmethionine (SAM) metabolism.

Methods Thirty-six Wistar rats were randomly divided into six groups, six rats in each group, half male and half female. The low, medium, and high dose groups of sodium arsenite (NaAsO₂) were given 2.5, 5.0, and 10.0 NaAsO₂ mg·kg⁻¹ (body weight, thereafter), respectively; the control group was given 10 mL·kg⁻¹ deionized water; the Rosa roxburghii Tratt juice intervention group was given 10 mg·kg⁻¹ NaAsO₂ for 4 h and then 10 mL·kg⁻¹ Rosa roxburghii Tratt juice; the Rosa roxburghii Tratt juice control group was given 10 mL·kg⁻¹ Rosa roxburghii Tratt juice by gavage. All rats were gavaged once a day, 6 d per week for 4 months. Histopathological changes of rat liver were observed by hematoxylin-eosin (HE) staining. Total bile acids (TBA) and γ-glutamyl transpeptidase (γ-GT) were detected by enzyme cycle method and rate method, respectively. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS) was used to evaluate SAM and S-adenosylhomo cysteine (SAH) in rat liver. Real-time fluorescence quantitative reverse transcriptional PCR (RT-qPCR) was used to detect the mRNA expression levels of the genes of glycine-N-methyltransferase (Gnmt), nicotinamide-N-methyltransferase (Nnmt), and phosphatidylethano-lamine N-mathyltransferase (Pemt).

Results In the control group, the liver nuclei were stained clearly, the cytoplasm was stained uniformly, and the liver cords were arranged radially without inflammatory infiltration. In the low, medium, and high dose groups of NaAsO₂, hepatic sinusoidal dilation, congestion, and inflammatory infiltration were observed to different degrees. Compared with the control group, TBA in the medium and high dose groups of NaAsO₂, and γ-GT in the high dose group of NaAsO₂ were significantly increased (P<0.05). The levels of TBA and γ-GT raised with the increase of arsenic dose (P_trend<0.05). Compared with the control group, SAH content was significantly increased, SAM content and SAM/SAH were significantly decreased in the low, medium, and high dose groups of NaAsO₂ (P<0.05), and there was a dose-response relationship between dose of arsenic and SAM and between dose of arsenic and SAM/SAH (P_trend<0.05). Decreases of SAM and SAM/SAH were significantly correlated with increase of liver function indexes TBA (SAM: r=−0.569; SAM/SAH: r=−0.607) and γ-GT (SAM: r=−0.577; SAM/SAH: r=−0.622) (P<0.05) respectively. In addition, compared with the control group, the mRNA expression levels of Gnmt in the high dose group of NaAsO₂, and Nnmt and Pemt in the low, medium, and high dose groups of NaAsO₂ were significantly increased (P<0.05). The expression levels of these three genes increased in a dose-dependent manner with NaAsO₂ treatment (P_trend<0.05). Gnmt, Nnmt, and Pemt mRNA expressions were negatively correlated with SAM (r=−0.490, −0.567, −0.593) and SAM/SAH (r=−0.433, −0.564, −0.746) respectively (P<0.05). Compared with the high dose group of NaAsO₂, the hepatic sinusoidal dilation and inflammatory infiltration of liver cells in the Rosa roxburghii Tratt juice intervention group were alleviated; the γ-GT and TBA decreased significantly, and recovered to the level of the control group; the mRNA expression levels of Gnmt, Nnmt, and Pemt and the SAH content were significantly decreased, and SAM content and SAM/SAH were increased (P<0.05).

Conclusion Arsenic-induced liver injury in rats is closely related to increased expression of Gnmt, Nnmt, Pemt and SAM consumption. Rosa roxburghii Tratt juice may ameliorate arsenic-induced liver injury in rats by inhibiting the abnormal mRNA expression of Gnmt, Nnmt, and Pemt as well as overconsumption of SAM. This study provides a basis for prevention and treatment of arsenic-induced liver injury from the perspective of SAM maintenance.