Is human umbilical cord mesenchymal stem cell-derived conditioned medium effective against oxidative and inflammatory status in CCl4-induced acute liver injury?

INTRODUCTION: Acute liver injury (ALI) is diagnosed by detection of elevated liver enzymes within six months after liver damage. Mesenchymal stem cells (MSCs) have recently been considered a beneficial strategy for treating various diseases due to healing secretory factors. Therapeutic effects of human umbilical cord MSCs-derived conditioned medium (hMSC-CM) were evaluated on CCl4-induced ALI. MATERIALS AND METHODS: Twenty-four male Wistar rats were divided into groups including N (received saline), ALI (received CCl4), RPMI (received CCl4 and RPMI medium), and ALI-CM (received CCl4 and hMSC-CM) groups. The expression of TNF-α and TGFß-1 genes was evaluated with qPCR. Hepatic levels of TNF-α and TGF-ß were measured by ELISA. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), glutathione peroxidase (GPx) activity, and catalase (CAT) activity were also assayed. Hematoxylin-eosin (H&E), Masson's trichrome, reticulin, and Periodic Acid-Schiff (PAS) stainings were conducted to evaluate tissue lesions. RESULTS: CCl4 increased expression of TNF-α and TGF-1ß at both mRNA and protein levels, while hMSC-CM decreased these parameters in the ALI-CM group. TAC levels significantly decreased in the ALI group, and CCl4 increased TOS and MDA levels compared with the N group. hMSC-CM treatment led to the return of these parameters to their baseline levels. GPx and CAT activity in the ALI group were significantly lower than in the N group and hMSC-CM reduced these parameters to the baseline in the ALI-CM group. hMSC-CM modulated CCl4-induced tissue lesions. CONCLUSION: The present study suggests hMSC-CM probably improves CCl4-induced ALI through its antioxidant and anti-inflammatory effects.

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis.

It has been shown that both nilotinib as a tyrosine kinase inhibitor, and atorvastatin as a rho-kinase inhibitor, have antifibrotic effects. Therefore, considering the relationship between these two pathways, this study aimed to investigate the effects of their co-treatment against hepatic stellate cells (HSCs) activation and liver fibrosis. For this purpose, the activation of HSCs coincided with these therapies. Also, liver fibrosis by carbon tetrachloride (CCl4 ) was induced in male Wistar rats and treated simultaneously with these compounds. The expression of alpha-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), Ras homolog gene family, and member A (RhoA)/Rho-associated protein kinase (ROCK) in HSCs were measured. The expression of transforming growth factor beta-1 (TGF-ß1), its receptor (TßRII), CTGF, and platelets derived growth factor (PDGF), in the livers, were also investigated, all by real-time PCR and western blot analysis. Also, histopathologic and immunohistochemical evaluations were performed to evaluate changes in liver fibrosis during treatment. The results indicated the down-regulation of RhoA/ROCK, CTGF, and α-SMA, and inhibition of the HSCs activation toward myofibroblasts. The results also showed that the combined use of atorvastatin and nilotinib has significantly higher inhibitory effects. The antifibrotic effects of atorvastatin and nilotinib co-administration were also observed by histopathologic and immunohistochemical observations, and inhibiting the expression of TGF-ß1, TßRII, CTGF, and PDGF. Taken together, this study revealed that co-administration of nilotinib-atorvastatin has novel antifibrotic effects, by inhibiting RhoA/ROCK, and CTGF pathway. Therefore, the importance of the common pathway of RhoA/ROCK and CTGF, in reducing fibrosis may almost be concluded.

Antiglycation and antioxidant activity of four Iranian medical plant extracts.

OBJECTIVE: Diabetes mellitus (DM) is the most common metabolic disorder that defined by chronic hyperglycemia for the deficiency in insulin secretion or resistance. Hyperglycemia could induce non-enzymatic glycation of proteins. It has been suggested that some traditional plants can improve blood glucose and inhibit glycation process. This work evaluates and compares the anti-glycation activities of four Iranian plant extracts in vitro. METHODS: The methanolic extract of "Fumaria officinalis, Stachys lavandulifolia, Salvia hydrangea and Rosa Damascene" was prepared in three different concentrations. Phenolic, flavonoids content and antioxidant activity were evaluated. The multistage glycation markers-fructosamines (early stage), protein carbonyls (intermediate stage) and ß aggregation of albumin were investigated in the bovine serum albumin (BSA)/ glucose systemt. RESULTS: All plants showed the high potency of scavenging free radicals and glycation inhibition in the following order: Fumaria officinalis> Rosa Damascene> Stachys lavandulifolia > Salvia hydrangea. There was a significant correlation between antioxidant and anti-glycation activity. Also, the antioxidant and anti-glycation capacity of extracts correlated with total phenolic and flavonoids content. CONCLUSION: Our findings demonstrated that the studied plants are good sources of anti-glycation and antioxidant compounds and, these properties can primarily attributable to phenolics, particularly flavonoids.

Hepatoprotective effects of Vaccinium arctostaphylos against CCl4-induced acute liver injury in rats.

BACKGROUND: This study was carried out to evaluate the antioxidant and hepatoprotective effects of Vaccinium arctostaphylos (V.a) methanolic extract on carbon tetrachloride (CCl4)-induced acute liver injury in Wistar rats. METHODS: Total phenolic and total flavonoid contents as well as antioxidant activity of V.a were determined. Extracts of V.a at doses of 200 and 400 mg/kg were administered by oral gavage to rats once per day for 7 days and then were given an intraperitoneal injection of 1 mL/kg CCl4 (1:1 in olive oil) for 3 consecutive days. Serum biochemical markers of liver injury, oxidative markers, as well as hydroxyproline (HP) content and histopathology of liver were evaluated. RESULTS: The obtained results showed that V.a had strong antioxidant activity. Treatment of rats with V.a blocked the CCl4-induced elevation of serum markers of liver function and enhanced albumin and total protein levels. The level of hepatic HP content was also reduced by the administration of V.a treatment. Histological examination of the liver section revealed that V.a prevented the occurrence of pathological changes in CCl4-treated rats. CONCLUSIONS: These findings suggested that V.a may be useful in the treatment and prevention of hepatic injury induced by CCl4.