Project Title

The Role of CYP2A5 and PPAR-alpha in Cadmium-induced liver injury

Authors' Affiliations

Julia Salamat (1) and Dr. Yongke Lu (2) (1) Department of Biological Sciences, College of Arts and Sciences, ETSU (2) Department of Health Sciences, College of Public Health, ETSU

Location

Ballroom

Start Date

4-5-2018 8:00 AM

End Date

4-5-2018 12:00 PM

Poster Number

87

Name of Project's Faculty Sponsor

Dr. Yongke Lu

Faculty Sponsor's Department

Health Sciences Department

Type

Poster: Competitive

Classification of First Author

Graduate Student-Master’s

Project's Category

Biomedical and Health Sciences

Abstract Text

Cadmium (Cd) is present in food at low levels, particularly in crops and is also present in groundwater. Cd can also be obtained from tobacco smoking and occupational exposure. Cd is not effectively excreted from the body. The primary organ that accumulates Cd is liver. Liver is the main organ involved in metabolizing exogenous chemicals. While metabolism of chemicals causes detoxification, it can also result in liver oxidative damage.

CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver. CYP2A6 expression is increased in patients with alcoholic or non-alcoholic fatty liver. Alcohol feeding induced CYP2A5 in mice and alcohol-induced fatty liver disease was enhanced in CYP2A5 knockout (CYP2A5-/-) mice, suggesting a protective effect of CYP2A5 on alcoholic fatty liver disease. PPAR-alpha, a transcription factor, is a major regulator of lipid metabolism in the liver.  CYP2A5 and PPAR-alpha are suggested to work together in regulation of lipid metabolism and in protection against alcoholic fatty liver. It is also suggested that CYP2A5 along with PPAR-alpha protects against high fat diet induced metabolic syndrome.

Cadmium can also induce CYP2a5 in mice. Recently it was discovered that there is a positive relation between soil heavy metals and fatty liver disease. Exposure to Cadmium leads to lipid accumulation in the liver, which can eventually lead to the development of Non-Alcoholic Fatty Liver Disease (NAFLD). In this study, the effects of CYP2A5 and PPAR-alpha on the acute cadmium-induced liver injury were tested using CYP2A5-/- mice and PPAR-alpha knockout (PPARα -/-) mice and CYP2A5 and PPAR-alpha wild-type mice.

Cadmium chloride (CdCl2) was administered intraperitoneally at 5 mg/kg body weight. A control group of mice were injected saline for comparison. The mice were sacrificed after 24 hours of injection. Blood was collected to test for markers indicative of liver disease such as ALT and AST levels, triglyceride levels, and blood glucose levels. The liver was collected to examine the liver damage by biochemical assays and pathological evaluation.

Both CYP2A5-/- and PPARα -/- mice exhibited less severe liver injury compared to their wild-type counterparts. These results suggest that despite the beneficial roles of both CYP2A5 and PPAR-alpha towards alcohol-induced liver injury and metabolic syndrome, they are not protective against Cd-induced liver injury.

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Apr 5th, 8:00 AM Apr 5th, 12:00 PM

The Role of CYP2A5 and PPAR-alpha in Cadmium-induced liver injury

Ballroom

Cadmium (Cd) is present in food at low levels, particularly in crops and is also present in groundwater. Cd can also be obtained from tobacco smoking and occupational exposure. Cd is not effectively excreted from the body. The primary organ that accumulates Cd is liver. Liver is the main organ involved in metabolizing exogenous chemicals. While metabolism of chemicals causes detoxification, it can also result in liver oxidative damage.

CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver. CYP2A6 expression is increased in patients with alcoholic or non-alcoholic fatty liver. Alcohol feeding induced CYP2A5 in mice and alcohol-induced fatty liver disease was enhanced in CYP2A5 knockout (CYP2A5-/-) mice, suggesting a protective effect of CYP2A5 on alcoholic fatty liver disease. PPAR-alpha, a transcription factor, is a major regulator of lipid metabolism in the liver.  CYP2A5 and PPAR-alpha are suggested to work together in regulation of lipid metabolism and in protection against alcoholic fatty liver. It is also suggested that CYP2A5 along with PPAR-alpha protects against high fat diet induced metabolic syndrome.

Cadmium can also induce CYP2a5 in mice. Recently it was discovered that there is a positive relation between soil heavy metals and fatty liver disease. Exposure to Cadmium leads to lipid accumulation in the liver, which can eventually lead to the development of Non-Alcoholic Fatty Liver Disease (NAFLD). In this study, the effects of CYP2A5 and PPAR-alpha on the acute cadmium-induced liver injury were tested using CYP2A5-/- mice and PPAR-alpha knockout (PPARα -/-) mice and CYP2A5 and PPAR-alpha wild-type mice.

Cadmium chloride (CdCl2) was administered intraperitoneally at 5 mg/kg body weight. A control group of mice were injected saline for comparison. The mice were sacrificed after 24 hours of injection. Blood was collected to test for markers indicative of liver disease such as ALT and AST levels, triglyceride levels, and blood glucose levels. The liver was collected to examine the liver damage by biochemical assays and pathological evaluation.

Both CYP2A5-/- and PPARα -/- mice exhibited less severe liver injury compared to their wild-type counterparts. These results suggest that despite the beneficial roles of both CYP2A5 and PPAR-alpha towards alcohol-induced liver injury and metabolic syndrome, they are not protective against Cd-induced liver injury.