Repurposing of Strychnine as the Potential Inhibitors of Aldo-keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis.

AKR1B1 and AKR1B10 are important members of aldo-keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism. These enzymes are involved in various metabolic processes, including the synthesis and metabolism of hormones, detoxification of reactive aldehydes, and the reduction of various endogenous and exogenous compounds. This study aimed to explore the potential of strychnine as an anticancer agent by targeting AKR1B1 and AKR1B10 via drug repurposing approach. To assess the drug-like properties of strychnine, a physiologically based pharmacokinetic (PKPB) model and High Throughput Pharmacokinetics (HTPK) approach were employed. The obtained results fell within the expected range for drug molecules, confirming its suitability for further investigation. Additionally, density functional theory (DFT) studies were conducted to gain insight into the electronic properties contributing to the drug molecule's reactivity. Building upon the promising DFT results, molecular docking analysis using the AutoDock tool was performed to examine the binding interactions between strychnine and the proposed targets, AKR1B1 and AKR1B10. Findings from the molecular docking studies suggested a higher probability of strychnine acting as an inhibitor of AKR1B1 and AKR1B10 with docking scores of - 30.84 and - 29.36 kJ/mol respectively. To validate the stability of the protein-ligand complex, Molecular Dynamic Simulation (MDS) studies were conducted, revealing the formation of a stable complex between the enzymes and strychnine. This comprehensive approach sheds light on the potential effectiveness of strychnine as a treatment for breast, lung, liver, and pancreatic cancers, as well as related malignancies. The novel insights gained from the physiologically based pharmacokinetic modeling, density functional theory, molecular docking, and molecular dynamics simulations collectively support the prospect of strychnine as a promising molecule for anticancer therapy. Further investigations are warranted to validate these findings and explore the therapeutic potential of strychnine in preclinical and clinical settings.

Experimental investigations of arsenic adsorption from contaminated water using chemically activated hematite (Fe2O3) iron ore.

Indigenous hematite iron ore was chemically activated as a function of various hydrogen peroxide concentrations (0.5, 1, 1.5, and 2.0 M), activation time, and iron ore size. Adsorption potential was evaluated at various initial arsenic concentrations, contact time, adsorbent dose, and particle size. Maximum 95% removal efficiency was achieved at 600-µm size of iron ore, activated with 0.5 M concentration of hydrogen peroxide at 24 h of activation time. The experimental data were further evaluated through Langmuir and Freundlich isotherms. The maximum 14.46 mg/g of adsorption capacity was observed through Langmuir isotherm. Moreover, adsorption kinetics was evaluated using pseudo-first-order and pseudo-second-order kinetics, and the intra-particle diffusion model. The kinetics of arsenic adsorption was best described by using the pseudo-first-order kinetics with a kinetic rate of 0.621 min-1. The hematite iron ore before and after arsenic adsorption was characterized by XRD, SEM, and EDX.

Evaluation of zinc, copper and iron in biological samples (scalp hair, blood and urine) of tuberculosis and diarrhea male human immunodeficiency virus patients.

BACKGROUND: The consequence of a deficiency in trace elements has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. This study examined the association between low scalp hair and blood zinc, copper, and iron concentrations and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). METHODS: The study was performed on sixty two male HIV+ patients (HIV-1) from different cities in Pakistan. The patients were divided in two groups according to secondary infections (tuberculosis, diarrhea and high fever). The biological samples (scalp hair, blood, and urine) were collected from AIDS patients. For comparative study, 120 healthy subjects (males) of the same age group (31 - 45 years), socio-economic status, localities, and dietary habits were also included. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked using certified reference materials (CRMs) and values obtained by conventional wet acid digestion method of the same CRMs. RESULTS: The results indicated significantly lower levels of Fe and Zn and high levels of Cu in the biological samples (blood and scalp hair) of male HIV-1 patients compared with control subjects. It was observed that the low levels of zinc and iron may be predictors for secondary infections in HIV-1 patients. There was a significant decrease in mean values of Fe and Zn in whole blood and scalp hair samples of three groups of AIDS patients as compared to a control healthy male group (p < 0.001). CONCLUSIONS: Deficiency of Zn and Fe might play a role in the development of AIDS in the subjects of this study.

Case-control study of male cancer patients exposed to arsenic-contaminated drinking water and tobacco smoke with relation to non-exposed cancer patients.

The investigated data indicated that inorganic arsenic in drinking water is associated with increased mortality from different types of cancers. In the present study, biological samples (blood and scalp hair) of male subjects having lung and bladder cancers and non-cancerous subjects belonging to arsenic (As)-exposed area of southern parts of Pakistan were analysed for As contents. The As levels in drinking water of understudy area showed that sections of understudy population are exposed to arsenic concentrations, which was 3-15-fold higher than the permissible level (<10 µg/L). For comparative purposes the biological samples of matched male cancer patient, as referent patients belonging to big city (Hyderabad) who had used municipal treated water with low arsenic levels <10 µg/L, were also collected. The exposed cancer patients have 2-3-fold higher level of As in both biological samples compared to non-exposed case-matched cancerous male subjects. This study is compelling evidence in support of positive associations between arsenic-contaminated water, food and cigarette with different types of risks of cancer.

Comparative study of liver cancer patients in arsenic exposed and non-exposed areas of Pakistan.

The investigated data shows that arsenic (As) in drinking water is associated with increased mortality from different types of cancers including liver cancer. In this study, blood and scalp hair samples of male liver cancer patients and healthy referents belonging to As exposed areas of Sindh Pakistan were analyzed for As contents. The As levels in drinking water of understudy area showed that sections of this population was exposed to 3-15-folds higher concentrations of As than permissible limit. For comparative purposes, blood and scalp hair samples of matched cancerous patient as referent patients belonging to big city (Hyderabad) who have used municipal treated water with low As levels <10 µg/L were also collected. The results of this study showed that the average As concentration was higher in the blood and scalp hair of exposed and non-exposed referent cancer patients as compared to referents (p < 001). The exposed cancerous patients have twofolds higher As level in both biological samples as related to non-exposed case matched cancerous male subjects.

Evaluation of status of cadmium, lead, and nickel levels in biological samples of normal and night blindness children of age groups 3-7 and 8-12 years.

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood trace metals toxicity, which is the most common problem found in underdeveloped countries. This study was designed to compare the levels of cadmium (Cd), lead (Pb), and nickel (Ni) in scalp hair, blood, and urine of night blindness children age ranged 3-7 and 8-12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of Cd, Pb, and Ni in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cd, Pb, and Ni by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cd, Pb, and Ni in the biological samples (blood, scalp hair, and urine) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating toxicity of trace metals in biological samples of night blindness children.

Interactions between cadmium and zinc in the biological samples of Pakistani smokers and nonsmokers cardiovascular disease patients.

The pathogenesis of some cardiovascular diseases (CVDs) has been altered with changes in the balance of certain trace and toxic elements. The aim of the present study was to assess the role of zinc (Zn) and cadmium (Cd) in smoker and nonsmoker male CVD patients (n = 457) of two age groups (31-45) and (46-60). The both elements were determined in biological samples (scalp hair, blood, and urine) of CVD patients and healthy referents for comparison purpose. The concentrations of Zn and Cd were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. It was observed that the mean values of Cd were significantly higher in the biological samples of smokers CVD as compared to nonsmoker CVD patients, while the level of Zn was lower in both smoker and nonsmoker patients. The concentrations of Zn in whole blood and scalp hair samples were lower in CVD patients as compared to referents (p > 0.001). Results showed significant changes of levels of Cd and Zn in blood and scalp hair samples of CVD patients when compared with healthy referents, while reverse in the case of urine samples. It was observed that low Zn levels were associated with both smoker and nonsmoker CVD patients, while increased cadmium accumulation was observed in smoker patients as compared to nonsmoker patients (p > 0.025).

Evaluation of cadmium, chromium, nickel, and zinc in biological samples of psoriasis patients living in Pakistani cement factory area.

Psoriasis is a noncontiguous common and chronic skin disorder. The aim of the present study was to compare the level of trace elements cadmium (Cd), chromium (Cr), Nickel (Ni), and zinc (Zn) in biological samples (whole blood, urine, and scalp hair) of psoriasis patients of both gender age ranged (25-55 years) at mild, moderate severe, and more severe stage (n = 418) living in the vicinity of cement factory. For comparison purposes, healthy age-matched referent subjects, residents of industrial and non-industrial area, of both gender were also selected (n = 241). The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The validity and accuracy of methodology was checked by using certified reference materials (CRMs) and conventional wet acid digestion method on same CRMs and real samples. The results of this study showed that the mean values of Cd, Cr, Ni, and Pb were significantly higher in scalp hair, blood, and urine samples of mild and severe psoriasis patients as compared to referents (p < 0.001), while the concentration of Zn was lower in the scalp hair and blood, but higher in the urine samples of psoriasis patients. The deficiency of Zn in psoriasis patients may be undoubtedly caused by the toxic element exposures via cement factory.

Evaluation of status of zinc, copper, and iron levels in biological samples of normal children and children with night blindness with age groups of 3-7 and 8-12 years.

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. This study was designed to compare the levels of zinc (Zn), copper (Cu), and iron (Fe) in scalp hair, blood, and urine of both genders of children with night blindness with age range of 3-7 and 8-12 years, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of zinc, copper, and iron in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cu, Fe, and Zn by flame atomic absorption spectrometry using an air/acetylene flame. The results indicated significantly lower levels of Fe, Cu, and Zn in the biological samples (blood and scalp hair) of male and female children with night blindness, compared with control subjects of both genders. These data present guidance to clinicians and other professionals investigating the deficiency of essential trace metals in biological samples (scalp hair and blood) of children with night blindness.

Distribution of copper, iron, and zinc in biological samples (scalp hair, serum, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls.

The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n = 521) of both gender age ranged 31-45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.

Evaluation of arsenic, cadmium, lead, nickel, and zinc in biological samples (scalp hair, blood, and urine) of tuberculosis and diarrhea male human immunodeficiency virus patients.

BACKGROUND: The consequence of a deficiency in trace elements has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. This study examined the association between high scalp hair and blood arsenic, cadmium, lead, and nickel concentrations and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). METHODS: The study was performed on sixty two male HIV+ patients (HIV-1) from different cities of Pakistan. The patients were divided in two groups according to secondary infections (tuberculosis, diarrhea, and high fever). The biological samples (scalp hair, blood, and urine) were collected from AIDS patients, and for comparative study 120 healthy subjects (males) of same age group (31 - 45 years), socio-economic status, localities, and dietary habits were also included. The elements in the biological samples were analyzed by electrothermal atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked using certified reference materials (CRMs) and with values obtained by conventional wet acid digestion method on same CRMs. RESULTS: The results indicated significantly higher levels of As, Cd, Ni, and Pb in the biological samples (scalp hair, blood, and urine) of male HIV-1 patients, compared with control subjects. It was observed that the high levels of these toxic elements may be predictors for secondary infections in HIV-1 patients. There was a significant increase in mean values of As, Cd, Ni, and Pb in whole blood, scalp hair, and urine samples of three groups of AIDS patients as compared to a controlled healthy male group (p < 0.001). CONCLUSIONS: These data present guidance to clinicians and other professionals investigating toxicity of As, Cd, Ni, and Pb in biological samples of AIDS patients.

Evaluation of toxic risk assessment of arsenic in male subjects through drinking water in southern Sindh Pakistan.

The arsenic (As) hazardous quotient was estimated based on concentration of As in drinking water and scalp hair of male subjects of two age groups (n=360) consuming As contaminated water at different levels and non-contaminated drinking water. The total As concentrations in drinking water of less-exposed (LE) and high-exposed (HE) areas was found to be 3- to 30-fold higher than the permissible limit of the World Health Organization (2004) for drinking water, while the levels of As in drinking water of non-exposed (NE) areas was within the permissible limit. The levels of As in scalp hair samples of male subjects of two age groups belonging to NE, LE, and HE areas ranged from 0.01 to 0.27, 0.11-1.31, and 0.36-6.80 µg/g, respectively. A significant correlation between As contents of drinking water and As concentration in scalp hair was observed in sub-district Gambit (r=0.825-0.852, p<0.001) as compared to those subjects belonging to LE sub-district Thari Mirwah. A toxicity risk assessment provides a hazard quotient corresponding to <10 that indicates non-carcinogenic exposure risk of understudy areas.

Evaluation of iodine, iron, and selenium in biological samples of thyroid mother and their newly born babies.

BACKGROUND: There is accumulating facts that the metabolism of essential trace elements is altered in thyroid patients. AIM: The aim of present study was to compare the status of essential trace elements, iodine, iron (Fe), and selenium (Se) in biological samples (serum and urine) of goitrous mothers (age ranged 30-40) and their newly born infants (n=76). An age matched 68 non-goitrous mothers and their infants, residing in the same locality, were selected as referents. For a comparative study, the biological samples of non-goitrous and goitrous pregnant and non pregnant female subjects of the same age group and socio-economic status were also analyzed. METHODS: The Fe and Se concentrations in biological samples were determined by a flame and hydride generation atomic absorption spectrometry respectively, while iodine was measured by iodide-ion selective electrode, prior to microwave assisted acid digestion. The validity and accuracy of the methodology was checked by certified reference materials. RESULTS: The mean values of iodine, Fe and Se in serum and urine samples of thyroid mothers and their infants were significantly lower as compared to the referent mothers-infants pairs (p<0.01). CONCLUSIONS: The deficiencies of essential trace elements may adversely affect the health of women and their neonates.

Microwave-assisted acid extraction of selenium from medicinal plants followed by electrothermal atomic absorption spectrometric determination.

A simple and rapid microwave-assisted extraction (MAE) of selenium (Se) from medicinal plants was investigated using different concentrations of nitric acid and hydrochloric acid, sample mass, heating time, microwave energy, and plant particle size. The optimization strategy was carried out using multivariate methodologies. Electrothermal atomic absorption spectrometry was used to determine Se. The accuracy of the optimized procedure was evaluated by using certified reference materials with certified values for Se and a microwave-assisted acid digestion (MD) method for comparative purpose. No significant difference was observed (P > 0.05) when comparing the values obtained by the proposed MAE and MD methods (paired t-test). Under the optimum operating conditions, the LOD obtained from the standard calibration curve was 0.012 microg/L for Se. The average RSD of the MAE method varied between 4.05 and 7.53% (n = 6). The proposed method was successfully applied for the determination of Se in medicinal plants used as remedies for cancerous and infection diseases.

Evaluation of cadmium and zinc in biological samples of tobacco and alcohol user male mouth cancer patients.

There is compelling evidence in support of positive associations between zinc (Zn) deficiency and high accumulation of cadmium (Cd) in biological samples of different cancerous patients. The incidence of mouth cancer has been increased among people who possess habit of drinking alcohol, tobacco smoking and chewing with gradients in Pakistan. In the present study, Cd and Zn contents of blood and scalp hair samples of 92 male mouth cancer patients and 78 referents of same age group (range 35-65 years), socio-economic status, localities and dietary habits. Among referent male subjects, 56 consumed tobacco (smoking/chewing), 22 had none of smoking and chewing tobacco habits, while none of them admitted for alcohol drinking. The scalp hair and whole blood samples were oxidized by 65% nitric acid and 30% hydrogen peroxide (2:1) ratio in microwave oven. The Zn in digests was determined by flame atomic absorption while Cd was determined by electrothermal atomic absorption spectrometry. The average Cd concentration was higher, while level of Zn was lower in the blood and scalp hair samples of mouth cancer patients as compared to referent subjects (p < .001). The male referents consuming tobacco (chewing and smoking) have high level of Cd in both their biological samples as compared to those not smoking or chewing tobacco (p < .012). The Cd/Zn ratio in both biological samples was found to be higher in patients than in referent subjects.

Interaction of cadmium and zinc in biological samples of smokers and chewing tobacco female mouth cancer patients.

Epidemiologic studies suggest that zinc (Zn) deficiency and high accumulation of cadmium (Cd) may be associated with increased risk of cancer. The incidence of mouth cancer has increased among females, who possess habits of chewing tobacco with gradients (areca nut and betel quid) and smoking tobacco in Pakistan. In present study, we measured the concentration of Cd and Zn in 96 mouth cancer patients (MCPs) and 110 female controls/referents (67 smoker and chewing tobacco), while 43 have none of smoking and chewing tobacco habits, belongs to different cities of Pakistan. Both controls and patients have same age group (ranged 35-65 years), socio-economic status, localities and dietary habits. The Zn and Cd were determined by flame/graphite furnace atomic absorption spectrophotometer, prior to microwave assisted acid digestion method. The Cd/Zn ratio in both biological samples was also calculated. The results of this study showed that the mean value of Zn was lower, while the mean concentration of Cd was higher in the blood and scalp hair samples of MCPs as compared to control subjects (p<0.001). The controls chewing and smoking tobacco have high level of Cd in both biological samples as compared to those have not smoking or chewing tobacco (p<0.012). The Cd/Zn ratio was higher in MCPs than control subjects. This study is compelling evidence in support of positive associations between cadmium, cigarette smoking, deficiency of Zn and cancer risk.

Interaction of copper with iron, iodine, and thyroid hormone status in goitrous patients.

In many developing countries, men and women are at high risk of goiter and iron deficiency. The aim of the recent study is to assess the interaction of (Cu), with iron (Fe), iodine/iodide (I), and thyroid hormones in goitrous patients. Sixty goitrous male (GMPs) and 72 female patients (GFPs) were evaluated for the Cu, Fe, I, and thyroid hormones status in biological samples (serum and urine), and compared to non-goitrous subjects of both genders (M = 106, F = 120). The biological samples were analyzed for Cu and Fe concentration using atomic absorption spectrometer, while I was measured by the potentiometric method, prior to microwave-assisted acid digestion (MD). Quality control for the method was established with certified samples. Significantly higher mean values of Cu in serum, and urine samples of GMPs and GFPs, while lower value of Fe and I were observed as compared to control subjects (p < 0.015), respectively. The mean values of free triiodothyronine (FT3) and free thyroxin (FT4) were found to be lower in goitrous patients of both genders than in the age-matched healthy controls (p < 0.006 and 0.002), respectively, in contrast high mean values of thyroid-stimulating hormone (TSH) were detected in patients (p < 0.009), as compared to non-goitrous subjects. It was observed that the deficiencies of Fe, I, and thyroid hormone in goitrous patients could be influenced by efficiency of Cu.

Respiratory effects in people exposed to arsenic via the drinking water and tobacco smoking in southern part of Pakistan.

In this study, a survey has been conducted during 2005-2007 on surface and groundwater arsenic (As) contamination and its impact on the health of local population, of villages located on the banks of Manchar lake, southern part of Sindh, Pakistan. We have also assessed the relationship between arsenic exposure through respiratory disorders in male subjects with drinking water and smoking cigarettes made from tobacco grown in agricultural land irrigated with As contaminated lake water. The biological samples (blood and scalp hair) were collected from As exposed subjects (100% smokers) and age matched healthy male subjects (40.2% smoker and 59.8% non smokers) belong to unexposed areas for comparison purposes. The As concentration in drinking water (surface and underground water), agricultural soil, cigarette tobacco and biological samples were determined by electrothermal atomic absorption spectrometry. The range of As concentrations in lake water was 35.2-158 microg/L (average 97.5 microg/L), which is 3-15 folds higher than permissible limit of World Health Organization (WHO, 2004). While the As level in local cigarette tobacco was found to be 3-6 folds higher than branded cigarettes (0.37-0.79 microg/g). Arsenic exposed subjects (with and without RD) had significantly elevated levels of As in their biological samples as compared to referent male subject of unexposed area. These respiratory effects were more pronounced in individuals who had also As induced skin lesions. The linear regressions showed good correlations between As concentrations in water versus hair and blood samples of exposed subjects with and without respiratory problems.

Estimation of toxic metals in scalp hair samples of chronic kidney patients.

The determination of toxic metals (TMs) in the biological samples of human beings is an important clinical screening procedure. The aim of this work is to determine total content of TMs, aluminum (Al), cadmium (Cd), nickel (Ni), and lead (Pb) in scalp hair samples of chronic kidney male patients (CKPs) on maintenance hemodialysis, during the period of 2005-2007. The study included 115 CKPs (all smokers) and 150 controls or referents [82 (nonsmokers) and 68 (smokers)]. Both controls and patients (males) were of the same age group (ranged 25-55 years), socioeconomic status, localities, and dietary habits. The scalp hair samples were analyzed by electrothermal atomic absorption spectrometer, prior to microwave-induced acid digestion. The accuracy of the total Al, Cd, Ni, and Pb measurements was tested by simultaneously analyzing certified reference material (human hair NCS ZC81002). No significant differences were observed between the analytical results and the certified values (paired t test at p > 0.05). The levels of TMs in scalp hair samples of patients were found to be higher as compared to control nonsmoker and smokers. Moreover, the study shows that levels of Al, Cd, Ni, and Pb in scalp hair samples may be useful to evaluate the impact of cigarette smoking in kidney failure patients.

Determination of copper and iron in biological samples of viral hepatitis (A-E) female patients.

There is accumulative evidence that the metabolism of iron and copper is altered in viral hepatic diseases, and these nutrients might have specific roles in their pathogenesis and progress. The aim of present study was to compare the level of copper (Cu) and iron (Fe) in biological samples (serum, urine, and scalp hair) of female patients suffering from different viral hepatitis (A, B, C, D, and E; n = 253) of age range 31-45 years. For comparative study, 95 healthy females of the same age group residing in the same city were selected. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in sera and scalp hair samples of hepatitis patients than age-matched control subjects, while the difference was significant (p < 0.001), in the cases of viral hepatitis B and viral hepatitis C as compared to viral hepatitis A, D, and E. The urinary levels of these elements were found higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.