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Received: 25 August 2021

First Online: 18 March 2023

4. Discussion

: Cardiovascular disease is a major cause of death worldwide, particularly in countries with worse economic condition [CitationRef removed]. Many pathological factors affect these diseases for which pathogenesis is not yet known. Exposure to toxins in the environment, including lead and other metals, is avoidable. Despite the long period since the first report on the relationship between lead and cardiovascular disease, the contribution of lead to the burden of cardiovascular disease is still not completely understood [CitationRef removed]. Numerous studies have been conducted on the mechanism of the effect of lead on cardiovascular damage, especially lead-induced hypertension [CitationRef removed, CitationRef removed]. Lead increases systemic blood pressure by reducing the activity of the sodium-potassium pump and increasing intracellular calcium, decreasing NO, and modifying adrenergic system activity, and hypertrophy [CitationRef removed, CitationRef removed]. Lead damages the system by altering the function of neuronal and hormonal receptors in the arteries, increasing inflammatory factors, and activating apoptotic pathways in the heart and arteries. The increase in oxidative stress is responsible for many of the cardiovascular effects of lead. Even low levels of lead increase oxidative stress in endothelial cells, vascular smooth muscles, and myocytes [CitationRef removed, CitationRef removed].Lead increases lipid peroxidation by increasing free radicals and inactivating antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase, causing tissue damage [CitationRef removed, CitationRef removed]. Cardiac tissue is one of the tissues prone to oxidative damage caused by reactive oxygen species such as superoxide, peroxide, and hydroxyl, due to its continuous activity, limited cell proliferation, low antioxidant reserves, and inability to store oxygen. Oxidative stress can damage tissue through peroxidation lipids, proteins, and activation pathways that lead to apoptosis, as well as by increases in inflammatory factors [CitationRef removed, CitationRef removed]. Antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase also non-enzymatic agents such as glutathione and stress proteins are the most important antioxidants in the body to detoxify free radicals [CitationRef removed, CitationRef removed, CitationRef removed]. Depending on the materials presented, lead may cause irreparable damage to the heart tissue by increasing oxidative stress, which also leads to reduced intracellular antioxidant stores and the tissues with low capacity to repair and regenerate.Results of the present study demonstrated that lead increases lipid peroxidation and decreased antioxidants activity in the heart of lead-poisoned rats. In histological examination, the level of collagen in the heart of lead-exposed rats increased as well. Given the importance of oxidative stress in lead-induced damage, the use of factors that decrease oxidative stress or increase the antioxidants activity and amount can be effective in reducing this damage. Berberine is one of the substances known for its antioxidant activity [CitationRef removed].Berberine has been shown to improve many side effects of metabolic disorders [CitationRef removed]. The protective effects of berberine have also been proven in cardiovascular diseases, cancer, gastrointestinal disorders, and the nervous system [CitationRef removed]. In previous studies in this group, berberine decreased oxidative stress, cognitive impairment, and apoptosis during chronic cerebral ischemia [CitationRef removed, CitationRef removed]. Berberine has received a lot of attention in numerous studies on cardiovascular system because of its strong therapeutic effects in various cardiovascular diseases. Berberine improves endothelial function in the cardiovascular system by activating eNOS, reducing endothelin-1, inhibiting alpha-adrenergic receptors, which has been associated with decreased blood pressure and increased blood flow to tissues [CitationRef removed, CitationRef removed]. Berberine also reduces vascular damage as a result of poor metabolic conditions such as hyperglycemia and hypercholesterolemia by optimizing cellular metabolic activity, preventing inflammation and apoptosis, inhibiting the accumulation of intracellular oxidative stress [CitationRef removed]. The mechanism of the antioxidant and anti-inflammatory effects of berberine is complicated and not fully understood. It involves different kinases and signaling pathways such as AMPK, MAPKs, Nrf2, and Nf-Kb [CitationRef removed]. In addition to the antioxidant and anti-inflammatory effects of berberine, which can be effective in improving heart disorders, the role of berberine in lipid metabolism is also important in that it can affect cardiovascular function. Berberine increases the LDL receptors in hepatocytes, which can collect LDL from the blood. There was also a decrease in cholesterol absorption from the gastrointestinal tract and an increase in excretion due to the use of berberine [CitationRef removed]. Berberine also improved heart contractions, reduced fibrosis, and atrophy caused by hypertension [CitationRef removed]. The anti-fibrotic effects of berberine in the diabetic rat hearts have also been studied, and it was shown that berberine decreased cardiac fibrosis by reducing IGF1 receptors, which led to a decrease in tissue factors MMP-2 / MMP-4 [CitationRef removed]. Clinical trials have also examined the effects of berberine on heart failure. Two-week administration of berberine in people with heart failure improves the ejection fraction, reduces ventricular contractions, tachycardia, and vascular resistance, and finally reduces mortality due to heart failure and improves heart function [23].In concluding<b>,</b> the present study established that berberine decreased lipid peroxidation and cardiac fibrosis in lead-poisoned animals, which was associated with increased antioxidant activity in heart tissue. It can be concluded that berberine can reduce lipid peroxidation and eventually cardiac fibrosis by enhancing the antioxidants activity and reducing oxidative stress in lead-poisoned rats.<b>ACKNOWLEDGEMENTS</b>Information reported in this article was extracted from Master’s Thesis by the author, Marzieh Pourebrahimian, a master degree student in physiology.<b>CONFLICT OF INTEREST</b>The authors declare that they have no conflicts of interest<b>COMPLIANCE WITH ETHICAL STANDARDS</b>All procedures involving animals were approved by Ethics Committee of Yazd University of Medical Science which is in accordance with the US National Institutes of Health Publication guide for the care and use of laboratory animals. The ethics code has been recorded in the ethics committee as IR. SSU. MEDICINE. REC.1397.084.<b>FUNDING</b>The authors would like to thank the Shahid Sadoughi University of Medical Sciences and Health Services for funding this project.