Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU‐Induced Hepatopathy in Tumor‐Bearing Dogs

Abstract

Background: Increases in liver enzymes occur in up to 86% of dogs receiving CCNU and can result in treatment delay or early discontinuation of treatment. Denamarin contains S-adenosylmethionine and silybin, both of which have been investigated as treatments for various liver diseases.Hypothesis: Dogs on CCNU receiving Denamarin have lower alanine aminotransferase (ALT) activity than dogs not receiving Denamarin. Dogs on Denamarin are less likely to require treatment delay because of hepatopathy and are more likely to complete their prescribed course of CCNU.Animals: Dogs with lymphoma, mast cell tumor, or histiocytic sarcoma that were prescribed CCNU with or without corticosteroids and with normal ALT activity were eligible for enrollment.Methods: Dogs were prospectively randomized to receive either concurrent Denamarin during CCNU chemotherapy or to receive CCNU alone. Liver-specific laboratory tests were run before each dose of CCNU.Results: Increased liver enzyme activity occurred in 84% of dogs receiving CCNU alone and in 68% of dogs on concurrent Denamarin. Dogs receiving CCNU alone had significantly greater increases in ALT, aspartate aminotransferase, alkaline phosphatase, and bilirubin and a significantly greater decrease in serum cholesterol concentrations than dogs receiving concurrent Denamarin. Dogs receiving CCNU alone were significantly more likely to have treatment delayed or discontinued because of increased ALT activity.Conclusions: Increased liver enzyme activity occurs commonly in dogs receiving CCNU chemotherapy. These results support the use of concurrent Denamarin to minimize increased liver enzyme activity in dogs receiving CCNU chemotherapy. Denamarin treatment also increases the likelihood of dogs completing a prescribed CCNU course.

Protective effects of S-adenosylmethionine (SAMe) and silybin on hepatorenal and hemostatic functions in dogs with endotoxemia

“…Silybin is an active part of an extract from milk thistle, known as silymarin, and has been shown to support liver function by helping maintain a healthy oxidative balance (17,20). Although silymarin was reported to improve the rate of survival of LPS-treated mice (20), there is no evidence yet to support the use of SAMe, silybin, or both in dogs with endotoxemia.…”

“…and anticoagulant proteins (protein S, protein C, antithrombin). Thus, liver protection in the course of sepsis is crucial to decrease mortality (16,17). Recent studies showed that S-adenosylmethionine (SAMe) and silymarin could prevent liver injury in different clinical conditions (toxininduced hepatopathy and alcohol-induced hepatopathy) (17) by regulating cytokine responses to the primary insult (18).…”

“…SAMe is a compound that functions widely in the body as a group donor or enzymatic inducer during transmethylation, transsulfuration, and aminopropylation (17). The liver synthesizes the majority of SAMe in the body (17), and SAMe has been shown to be an important compound for liver health (17)(18)(19).…”

“…Thus, liver protection in the course of sepsis is crucial to decrease mortality (16,17). Recent studies showed that S-adenosylmethionine (SAMe) and silymarin could prevent liver injury in different clinical conditions (toxininduced hepatopathy and alcohol-induced hepatopathy) (17) by regulating cytokine responses to the primary insult (18). SAMe is a compound that functions widely in the body as a group donor or enzymatic inducer during transmethylation, transsulfuration, and aminopropylation (17).…”

“…Recent studies showed that S-adenosylmethionine (SAMe) and silymarin could prevent liver injury in different clinical conditions (toxininduced hepatopathy and alcohol-induced hepatopathy) (17) by regulating cytokine responses to the primary insult (18). SAMe is a compound that functions widely in the body as a group donor or enzymatic inducer during transmethylation, transsulfuration, and aminopropylation (17). The liver synthesizes the majority of SAMe in the body (17), and SAMe has been shown to be an important compound for liver health (17)(18)(19).…”