Role of zinc in health and disease.

This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.

Liver Iron Loading in Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) is a common chronic liver disease with increasing incidence worldwide. Alcoholic liver steatosis/steatohepatitis can progress to liver fibrosis/cirrhosis, which can cause predisposition to hepatocellular carcinoma. ALD diagnosis and management are confounded by several challenges. Iron loading is a feature of ALD which can exacerbate alcohol-induced liver injury and promote ALD pathologic progression. Knowledge of the mechanisms that mediate liver iron loading can help identify cellular/molecular targets and thereby aid in designing adjunct diagnostic, prognostic, and therapeutic approaches for ALD. Herein, the cellular mechanisms underlying alcohol-induced liver iron loading are reviewed and how excess iron in patients with ALD can promote liver fibrosis and aggravate disease pathology is discussed. Alcohol-induced increase in hepatic transferrin receptor-1 expression and up-regulation of high iron protein in Kupffer cells (proposed) facilitate iron deposition and retention in the liver. Iron is loaded in both parenchymal and nonparenchymal liver cells. Iron-loaded liver can promote ferroptosis and thereby contribute to ALD pathology. Iron and alcohol can independently elevate oxidative stress. Therefore, a combination of excess iron and alcohol amplifies oxidative stress and accelerates liver injury. Excess iron-stimulated hepatocytes directly or indirectly (through Kupffer cell activation) activate the hepatic stellate cells via secretion of proinflammatory and profibrotic factors. Persistently activated hepatic stellate cells promote liver fibrosis, and thereby facilitate ALD progression.

Iron and iron-related proteins in alcohol consumers: cellular and clinical aspects.

Alcohol-associated liver disease (ALD) is one of the most common chronic liver diseases. Its pathological spectrum includes the overlapping stages of hepatic steatosis/steatohepatitis that can progress to liver fibrosis and cirrhosis; both are risk factors for hepatocellular carcinoma. Moreover, ALD diagnosis and management pose several challenges. The early pathological stages are reversible by alcohol abstinence, but these early stages are often asymptomatic, and currently, there is no specific laboratory biomarker or diagnostic test that can confirm ALD etiology. Alcohol consumers frequently show dysregulation of iron and iron-related proteins. Examination of iron-related parameters in this group may aid in early disease diagnosis and better prognosis and management. For this, a coherent overview of the status of iron and iron-related proteins in alcohol consumers is essential. Therefore, here, we collated and reviewed the alcohol-induced alterations in iron and iron-related proteins. Reported observations include unaltered, increased, or decreased levels of hemoglobin and serum iron, increments in intestinal iron absorption (facilitated via upregulations of duodenal divalent metal transporter-1 and ferroportin), serum ferritin and carbohydrate-deficient transferrin, decrements in serum hepcidin, decreased or unaltered levels of transferrin, increased or unaltered levels of transferrin saturation, and unaltered levels of soluble transferrin receptor. Laboratory values of iron and iron-related proteins in alcohol consumers are provided for reference. The causes and mechanisms underlying these alcohol-induced alterations in iron parameters and anemia in ALD are explained. Notably, alcohol consumption by hemochromatosis (iron overload) patients worsens disease severity due to the synergistic effects of excess iron and alcohol.