Copper overdose
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Copper Overdose: Mechanisms, Effects, and Implications
Introduction to Copper Toxicity
Copper is an essential trace metal necessary for various biological functions. However, an excess of copper can lead to severe toxicity and organ dysfunction. This article synthesizes recent research on the mechanisms and effects of copper overdose, highlighting its impact on cellular processes and organ systems.
Mechanisms of Copper-Induced Cell Death
Mitochondrial Protein Aggregation and Cell Death
Excess copper can cause mitochondrial protein aggregation, leading to a unique form of cell death. This process involves the disruption of specific mitochondrial metabolic enzymes, which triggers cellular toxicity and death1. Understanding this mechanism is crucial for explaining the pathology associated with genetic copper overload disorders and exploring potential therapeutic applications, such as selectively targeting cancer cells with increased intracellular copper1.
Mitophagy and Endoplasmic Reticulum Stress
In animal studies, copper exposure has been shown to activate mitophagy and endoplasmic reticulum (ER) stress-mediated apoptosis. For instance, in chickens, excess copper led to vacuolar degeneration, mitochondrial swelling, and the formation of autophagosomes. This was accompanied by upregulation of mitophagy and ER stress markers, indicating a significant connection between copper toxicity and cerebrum damage5.
Organ Susceptibility to Copper Toxicity
Liver, Kidney, and Brain Dysfunction
Chronic exposure to copper, particularly in the form of copper sulfate, results in significant organ dysfunction. In a rat model, increased copper concentrations were observed in the liver, kidney, and brain, with the liver being the most affected organ. This exposure led to neurobehavioral abnormalities and liver and kidney dysfunctions, correlating with the copper levels in these organs2. The study highlighted that liver dysfunction was marked by elevated serum ALT, AST, and bilirubin levels, while kidney dysfunction was indicated by increased BUN levels2.
Acute Copper Sulfate Poisoning
Acute copper sulfate poisoning presents with severe clinical manifestations, including gastrointestinal symptoms and liver toxicity. Histopathological examinations in cases of acute poisoning revealed ulcerations in the gastric and intestinal mucosa, liver cell necrosis, and kidney damage, including glomerular congestion and tubular cell necrosis3. The severity of these manifestations correlated with elevated levels of serum and whole blood copper3.
Regulatory Health Criteria and Risk Assessment
Oral Reference Dose (RfD) for Copper
A critical review of copper exposure and its effects suggests that typical oral exposures are generally not a health concern. However, high levels of soluble copper salts can cause acute gastrointestinal symptoms and, in rare cases, liver toxicity. An alternative method using categorical regression analysis has been proposed to develop an optimal oral reference dose (RfD) for copper. This method considers deficiency, toxicity, and integrates data from human and animal studies, recommending an RfD of 0.04 mg Cu/kg/day to protect against acute and chronic toxicity4. This dose is not intended for individuals with rare genetic disorders related to copper sensitivity or those with excessive supplement intake4.
Conclusion
Copper overdose can lead to severe cellular and organ dysfunction, primarily affecting the liver, kidneys, and brain. Understanding the mechanisms of copper-induced toxicity, such as mitochondrial protein aggregation and ER stress-mediated apoptosis, is crucial for developing therapeutic strategies and regulatory guidelines. Further research is needed to refine the protective measures and treatment options for copper toxicity.
Sources and full results
Most relevant research papers on this topic
Copper-induced cell death
Excess copper accumulation disrupts specific mitochondrial metabolic enzymes, leading to a unique cell death mechanism that may explain genetic copper overload disorders and offer new cancer treatment options.
Highly CitedA study of dose response and organ susceptibility of copper toxicity in a rat model.
Chronic oral copper sulphate exposure at subtoxic levels leads to neurobehavioral abnormalities, liver and kidney dysfunctions, with the liver being the most vulnerable organ.
RCT
Animal StudyHighly CitedAcute copper sulfate poisoning.
Acute copper sulfate poisoning is a common and severe condition in India, with higher levels of copper in the blood correlating to severe symptoms and organ damage.
Highly CitedCritical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper
An oral reference dose of 0.04 mg Cu/kg/day is protective against acute or chronic toxicity in adults and children, considering deficiency, toxicity, and genetic susceptibility.
Literature ReviewHighly CitedExposure to copper activates mitophagy and endoplasmic reticulum stress‐mediated apoptosis in chicken (Gallus gallus) cerebrum
Excessive copper exposure can induce mitophagy and ER stress-mediated apoptosis in chicken cerebrum, providing a new insight into copper neurotoxicity.
RCTAnimal StudyAcute copper sulphate poisoning: a case report and literature review.
Copper sulphate poisoning can be treated with symptomatic treatment and specific copper chelation therapy, but the pathogenesis remains unclear and no single treatment is currently superior.
Case ReportHighly CitedGastric response to acute copper exposure.
Acute exposure to copper in water can modify the first phase of gastric emptying, with 9 subjects experiencing nausea after receiving 10 mg Cu/l of copper.
Zinc-induced copper deficiency in Wilson disease
Chronic therapeutic overdose of zinc can cause copper deficiency in Wilson disease patients, leading to haematological abnormalities and neurological complications.
Case ReportCopper Toxicity And Its Medicolegal Aspects:A Review
Copper toxicity can cause severe health effects, and its diagnosis requires close collaboration between forensic pathologists and toxicologists.
Acute cardiovascular toxic effects of copper in anesthetized rabbits.
Copper initially activates peripheral organs like the heart and then inhibits sympathetic outflow, leading to cardiotoxic effects in anesthetized rabbits.
Non-RCTAnimal Study