Antioxidant, Anti-inflammatory, and Genomic Stability Enhancement Effects of Zincl-carnosine: A Potential Cancer Chemopreventive Agent?

Abstract

Cancer is one of the major causes of death worldwide, and the incidence and mortality rates of cancer are expected to rise tremendously in the near future. Despite a better understanding of cancer biology and advancement in cancer management, current strategies in cancer treatment remain costly and ineffective. Hence, instead of putting more efforts to search for new cancer cures, attention has now been shifted to the development of cancer chemopreventive agents as a preventive measure for cancer formation. It is well known that neoplastic transformation of cells is multifactorial, and the occurrence of oxidative stress, chronic inflammation, and genomic instability events has been implicated in the carcinogenesis of cells. Zinc l-carnosine (ZnC), which is clinically used as gastric ulcer treatment in Japan, has been suggested to have the potential in preventing cancer development. Multiple studies have revealed that ZnC possesses potent antioxidant, anti-inflammatory, and genomic stability enhancement effects. Thus, this review provides some mechanistic insight into the antioxidant, anti-inflammatory, and genomic stability enhancement effects of ZnC in relevance to its chemopreventive potential.

A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice

“…Supplementation of carnosine in diabetic rodents increases renal carnosine concentrations [ 32 ] and consistently preserves renal morphology and function [ 20 ]. In humans carnosinemia, due to CN1 deficiency may be a non-disease; whereas accumulation of carnosine should protect against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes and chronic renal failure [ 3 , 20 ] and may prevent cancer development [ 33 ]. Efficacy of therapeutic carnosine supplementation in humans, however, is limited by a highly active serum CN1 largely preventing major increases in serum carnosine concentrations [ 27 ].…”

A Review of Zinc-L-Carnosine and Its Positive Effects on Oral Mucositis, Taste Disorders, and Gastrointestinal Disorders

“…In addition, a study using an acetic acid-induced rat model reported that the ZnC treatment group showed a significant antiulcer effect and healing action compared to the control [34]. These results are most likely a result of the anti-inflammatory and antioxidant functions of ZnC [35]. This function of ZnC helps to explain the many other benefits it can exert throughout the GI tract.…”

“…Several studies have suggested that ZnC reduces gastric lesions related to stomach ulcers and accelerates the healing process in animal models [31][32][33][34]. The primary mechanisms of action are thought to be related to its anti-inflammatory and antioxidant functions [35]. For example, in an ethano-induced rat model of gastric injury, inflammatory cytokines, such as interleukin-1β, interleukin-8, interleukin-6, and tumor necrosis factor, decreased in a dose-dependent manner in the group receiving ZnC when compared to the control group [31].…”

Zinc L-Carnosine Inhibits The Secretion of Pro-Inflammatory HMGB1 Protein From Lipopolysaccharide-Induced RAW 264.7 Murine Macrophage

“…Recently, the e cacy of ZnC in the treatment of oral mucositis, esophagitis, proctitis, and taste alterations resulting from chemotherapy or radiotherapy is widely studied as well [10,11]. The potent antioxidant and anti-in ammatory properties of ZnC has been proposed as the mechanisms of action of underlying such therapeutics effects of ZnC [11,12]. Previously, ZnC was reported to protect mice against lipopolysaccharide (LPS)-induced endotoxin shock [13].…”