Investigating the toxic mechanism of iron oxide nanoparticles-induced oxidative stress in tadpole (Duttaphrynus melanostictus): A combined biochemical and molecular study.

Metal oxide nanomaterials have toxicity towards aquatic organisms, especially microbes and invertebrates, but little is known about their impact on amphibians. We conducted a study on Duttaphrynus melanostictus (D. melanostictus) tadpoles to explore the chronic toxicity effects of iron oxide nanoparticles (IONPs) and the underlying mechanisms of IONPs-induced oxidative stress. IONPs exposure led to increased iron accumulation in the blood, liver, and kidneys of tadpoles, significantly affecting blood parameters and morphology. Higher IONPs concentrations (10 and 50 mg L-1) triggered reactive oxygen species generation, resulting in lipid peroxidation, oxidative stress, and pronounced toxicity in tadpoles. The activity levels of antioxidant enzymes/proteins (SOD, CAT, albumin, and lysozyme) decreased after IONPs exposure, and immunological measures in the blood serum were significantly reduced compared to the control group. Molecular docking analysis revealed that IONPs primarily attached to the surface of SOD/CAT/albumin/lysozyme through hydrogen bonding and hydrophobic forces. Overall, this study emphasizes the ability of IONPs to induce oxidative damage by decreasing immunological profiles such as ACH50 (34.58 ± 2.74 U mL-1), lysozyme (6.94 ± 0.82 U mL-1), total Ig (5.00 ± 0.35 g dL-1), total protein (1.20 ± 0.17 g dL-1), albumin (0.52 ± 0.01 g dL-1) and globulin (0.96 ± 0.01 g dL-1) and sheds light on their potential toxic effects on tadpoles.

Arsenic and adipose tissue: an unexplored pathway for toxicity and metabolic dysfunction.

Arsenic-contaminated drinking water can induce various disorders by disrupting lipid and glucose metabolism in adipose tissue, leading to insulin resistance. It inhibits adipocyte development and exacerbates insulin resistance, though the precise impact on lipid synthesis and lipolysis remains unclear. This review aims to explore the processes and pathways involved in adipogenesis and lipolysis within adipose tissue concerning arsenic-induced diabetes. Although arsenic exposure is linked to type 2 diabetes, the specific role of adipose tissue in its pathogenesis remains uncertain. The review delves into arsenic's effects on adipose tissue and related signaling pathways, such as SIRT3-FOXO3a, Ras-MAP-AP-1, PI(3)-K-Akt, endoplasmic reticulum stress proteins, CHOP10, and GPCR pathways, emphasizing the role of adipokines. This analysis relies on existing literature, striving to offer a comprehensive understanding of different adipokine categories contributing to arsenic-induced diabetes. The findings reveal that arsenic detrimentally impacts white adipose tissue (WAT) by reducing adipogenesis and promoting lipolysis. Epidemiological studies have hinted at a potential link between arsenic exposure and obesity development, with limited research suggesting a connection to lipodystrophy. Further investigations are needed to elucidate the mechanistic association between arsenic exposure and impaired adipose tissue function, ultimately leading to insulin resistance.

Silver nanoparticle ecotoxicity and phytoremediation: a critical review of current research and future prospects.

Silver nanoparticles (AgNPs) are widely used in various industries, including textiles, electronics, and biomedical fields, due to their unique optical, electronic, and antimicrobial properties. However, the extensive use of AgNPs has raised concerns about their potential ecotoxicity and adverse effects on the environment. AgNPs can enter the environment through different pathways, such as wastewater, surface runoff, and soil application and can interact with living organisms through adsorption, ingestion, and accumulation, causing toxicity and harm. The small size, high surface area-to-volume ratio, and ability to generate reactive oxygen species (ROS) make AgNPs particularly toxic. Various bioremediation strategies, such as phytoremediation, have been proposed to mitigate the toxic effects of AgNPs and minimize their impact on the environment. Further research is needed to improve these strategies and ensure their safety and efficacy in different environmental settings.

Autophagy Analysis: A Step-by-Step Simple Practical Guide for Immunofluorescence and Western Blotting.

Autophagy is a vital cellular process responsible for breaking down faulty cellular components and organelles, ultimately routed through lysosomes for degradation. This intricate mechanism involves the translocation of LC3, a cytoplasmic protein, onto the autophagosome membranes. As a result, it becomes feasible to discern cells engaged in autophagy by employing fluorescent markers designed for LC3 or other indicative autophagy markers. Although a variety of techniques such as immunofluorescence and western blotting serve as indispensable tools for assessing autophagy, the definitive confirmation comes from the visualization of autophagosomes using transmission electron microscopy. While numerous protocols for antibody staining can be found in scientific literature and on antibody suppliers' websites, these procedures often demand significant time and financial resources for setup. This chapter endeavors to provide a user-friendly and cost-effective guide for practitioners seeking proficiency in immunofluorescence staining and western blotting techniques.

A Review on Caspases: Key Regulators of Biological Activities and Apoptosis.

Caspases are proteolytic enzymes that belong to the cysteine protease family and play a crucial role in homeostasis and programmed cell death. Caspases have been broadly classified by their known roles in apoptosis (caspase-3, caspase-6, caspase-7, caspase-8, and caspase-9 in mammals) and in inflammation (caspase-1, caspase-4, caspase-5, and caspase-12 in humans, and caspase-1, caspase-11, and caspase-12 in mice). Caspases involved in apoptosis have been subclassified by their mechanism of action as either initiator caspases (caspase-8 and caspase-9) or executioner caspases (caspase-3, caspase-6, and caspase-7). Caspases that participate in apoptosis are inhibited by proteins known as inhibitors of apoptosis (IAPs). In addition to apoptosis, caspases play a role in necroptosis, pyroptosis, and autophagy, which are non-apoptotic cell death processes. Dysregulation of caspases features prominently in many human diseases, including cancer, autoimmunity, and neurodegenerative disorders, and increasing evidence shows that altering caspase activity can confer therapeutic benefits. This review covers the different types of caspases, their functions, and their physiological and biological activities and roles in different organisms.

Dietary phytoestrogen diosgenin interrupts metabolism, physiology, and reproduction of Swiss albino mice: Possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant.

Dietary phytoestrogens are the main source of environmental contamination due to their estrogen-mimicking and endocrine-disrupting effects, posing a threat to microbial, soil, plant, and animal health. Diosgenin, a phytosteroid saponin, is used in many traditional medicines, nutraceuticals, dietary supplements, contraceptives, and hormone replacement therapies against numerous diseases and disorders. It is important to be aware of the potential risks associated with diosgenin, as well as its potential to cause reproductive and endocrine toxicity. Due to the lack of research on the safety and probable adverse side effects of diosgenin, this work evaluated the endocrine-disrupting and reproductive toxicity of diosgenin in albino mice by following acute toxicity (OECD-423), repeated dose 90-day oral toxicity (OECD-468), and F1 extended one-generation reproductive toxicity (OECD-443) studies. Diosgenin was found to be slightly toxic, with LD50 for male and female mice being 546.26 and 538.72 mg/kg, respectively. Chronic exposure of diosgenin (10, 50, 100, and 200 mg/kg) generated oxidative stress, depleted antioxidant enzymes, disturbed homeostasis of the reproductive hormones, and interrupted steroidogenesis, germ cell apoptosis, gametogenesis, sperm quality, estrous cycle, and reproductive performance in the F0 and F1 offspring. Long-term oral exposure of diosgenin to the mice disturbed the endocrine and reproductive functions and generated transgenerational reproductive toxic effects in F0 and F1 offspring. These results suggest that diosgenin should be used carefully in food products and medical applications due to its potential endocrine-disrupting and reproductive toxic effects. The findings of this study provide a better understanding of the potential adverse effects of diosgenin and the need for appropriate risk assessment and management of its use.

Ecotoxicity risk assessment of copper oxide nanoparticles in Duttaphrynus melanostictus tadpoles.

In recent years, copper oxide nanoparticles (CONPs) have gained considerable importance in ecotoxicology studies. CONP ecotoxicity studies on amphibians are limited, particularly on Duttaphrynus melanostictus (D. melanostictus) tadpoles, and most CONP ecotoxicity studies have shown developmental effects on amphibians. Therefore, the present study aimed to determine the ecotoxicity of CONPs in D. melanostictus tadpoles by assessing multi-biomarkers including bioaccumulation, antioxidants, biochemical, haematological, immunological and oxidative stress biomarkers. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to characterize the morphology and physicochemical properties of CONPs. After 30 d of the experiment, blood and organs were collected to measure the levels of multiple biomarkers. The dissolution rate of copper ions in exposed media was observed in all studied groups. According to the results, significant (p < 0.05) increase in copper ion bioaccumulation (blood, liver and kidney), oxidative stress and biochemical biomarkers in the blood serum of CONPs exposed tadpoles compared to control tadpoles, which was accompanied by significant variations in morphological and haematological parameters. In contrast to the untreated tadpoles, the CONPs-exposed tadpoles showed statistically significant (p < 0.05) decreases in antioxidants and immunological indices of blood serum. Based on our results, we concluded that the ecotoxicity of CONPs is due to the production of reactive oxygen species (ROS), which can cause oxidative stress in tadpoles, resulting in impairments. According to our knowledge, the present study was the first to use a multi-biomarker ecotoxicity approach on D. melanostictus tadpoles that could be used as an ecological bioindicator to assess aquatic toxicity.

A review on chromium health hazards and molecular mechanism of chromium bioremediation.

Living beings have been devastated by environmental pollution, which has reached its peak. The disastrous pollution of the environment is in large part due to industrial wastes containing toxic pollutants. The widespread use of chromium (Cr (III)/Cr (VI)) in industries, especially tanneries, makes it one of the most dangerous environmental pollutants. Chromium pollution is widespread due to ineffective treatment methods. Bioremediation of chromium (Cr) using bacteria is very thoughtful due to its eco-friendly and cost-effective outcome. In order to counter chromium toxicity, bacteria have numerous mechanisms, such as the ability to absorb, reduce, efflux, or accumulate the metal. In this review article, we focused on chromium toxicity on human and environmental health as well as its bioremediation mechanism.

A review on arsenic pollution, toxicity, health risks, and management strategies using nanoremediation approaches.

OBJECTIVES: Over 50 countries are affected by arsenic contamination. The problem is becoming worse as the number of affected people increases and new sites are reported globally. CONTENT: Various human activities have increased arsenic pollution, notably in both terrestrial and aquatic environments. Contamination of our water and soil by arsenic poses a threat to our environment and natural resources. Arsenic poisoning harms several physiological systems and may cause cancer and death. Excessive exposure may cause toxic build-up in human and animal tissues. Arsenic-exposed people had different skin lesion shapes and were vulnerable to extra arsenic-induced illness risks. So far, research shows that varying susceptibility plays a role in arsenic-induced diseases. Several studies have revealed that arsenic is a toxin that reduces metabolic activities. Diverse remediation approaches are being developed to control arsenic in surrounding environments. SUMMARY AND OUTLOOK: A sustainable clean-up technique (nanoremediation) is required to restore natural equilibrium. More research is therefore required to better understand the biogeochemical processes involved in removing arsenic from soils and waters.

Chromium toxicity and its remediation by using endophytic bacteria and nanomaterials: A review.

Chromium (Cr) is a crucial element for all life forms. Various anthropogenic activities have been responsible for environmental contamination with Cr (VI) in recent years. For this review, articles were collected using electronic databases such as Web of Science, Pubmed, ProQuest, and Google Scholar as per the guidelines of PRISMA-2015, applying the Boolean search methods. Chromium can cause severe health complications in humans and animals and threatens the surrounding environment, with negative impacts on crop yield, development, and quality. Hence, monitoring Cr contamination is essential, and various remediation technologies have emerged in the past 50 years to reduce the amount of Cr in the environment. This review focuses on chromium exposure and the associated environmental health risks. We also reviewed sustainable remediation processes, with emphasis on nanoparticle and endophytic remediation processes.

Antioxidative, anti-inflammatory and anti-apoptotic action of ellagic acid against lead acetate induced testicular and hepato-renal oxidative damages and pathophysiological changes in male Long Evans rats.

Lead (Pb), is an environmental toxicant, causes multi-organ dysfunction including reproductive impairments. This study designed to investigate the prospective antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid (EA) on Pb-mediated testicular and hepato-renal toxicity. Four experimental groups of five male Long-Evans rats each were used: control, Pb (60 mg/kg), EA (30 mg/kg), and Pb + EA groups. All groups were given their respective treatment orally for 30 days. Pb exposure altered body and organs weight, food and water consumption, rectal temperature, Pb residue levels in tissues, liver and kidney function, sperm quality parameters, serum metabolic and hematology profiles, and impaired the oxidative/antioxidative balance in the testicular and hepato-renal tissue, as shown by the decreased antioxidant proteins (superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione) and increased the oxidative (MDA, lipid hydroperoxides, conjugated dienes, protein carbonyl, fragmented DNA and GSH:GSSG ratio) stress and inflammatory (IL-1, IL-6, TNF-α, prostaglandin, LTB4, NO, myeloperoxidase, LDH) markers. Moreover, a dysregulation in the stress response (HSP-70) and apoptotic-regulating proteins (BAX, BCL-2, and active Caspase-3) were recorded upon Pb exposure. Remarkably, EA oral administration reduced the Pb residue levels in tissues, improved the liver and kidney function, revived the spermatogenesis and sperm quality, restored redox homeostasis, suppressed the oxidative stress, inflammatory and apoptotic responses in the liver, kidney and testis tissue. Our findings point out that EA can be used as a phyto-chelator to overcome the adverse effects of Pb exposure due to its potent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Assessment of toxicity in the freshwater tadpole Polypedates maculatus exposed to silver and zinc oxide nanoparticles: A multi-biomarker approach.

Nanoparticles (NPs), especially silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs), are widely used in various industrial applications and are released into the surrounding environment through industrial and household wastewater. They have enormous toxic effects on aquatic animals and amphibians. In the current study, a multi-biomarker approach was used to assess toxicity on Polypedates maculatus (P. maculatus) tadpoles collected from a freshwater pond and exposed to sub-lethal concentrations of Ag-NPs (1, 5 and 10 mg L-1) and ZnO-NPs (1, 10 and 50 mg L-1). A significant bioaccumulation of silver (Ag) and Zinc (Zn) was observed in the blood, liver, kidney and bones in comparison to control tadpoles. Blood parameters (Red blood cells (RBC), Hematocrit (Htc), White blood cells (WBC), monocytes, lymphocytes and neutrophils), immunological markers (ACH50, lysozyme, total Ig, total protein, albumin, and globulin), biochemical markers (glucose, cortisol, cholesterol, triglycerides, alanine transaminase (ALT), asparatate transaminase (AST), alkaline phosphatase (ALP), urea and creatinine) and the oxidative stress marker (LPO) of serum were increased significantly (p < 0.05) in Ag/ZnO-NPs exposed groups when compared to the control groups. The levels of mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and haemoglobin (Hb) in the ZnO NP-exposed groups were significantly different from those in the control group. Antioxidant (SOD and CAT) levels were significantly declined in the treatment groups. Based on the results, Ag/ZnO-NPs are toxic to aquatic organisms and amphibians at sub-lethal concentrations. The species P. maculatus can be used as a bioindicator for the nanomaterial (NM) contamination of freshwater systems.

A systematic review report on tobacco products and its health issues in India.

India is the second country in tobacco production in the world. Smoking tobacco products included Hookah, Cohutta, Chillum, Chillum, ganja, Beedi, Mava, Cigarettes, and cigar etc. Various types of smokeless tobacco like betel quid, khaini, mishri, snuff, gutkha are used. Fifty percent of them are addicted to smokeless tobacco. Sixty eight smokeless tobacco products were available in 2010; most of them included the risk of cancer warning except for loose tobacco products. Women mostly prefer 8 out of 29 gutkha brands. Out of these 29 gutkha brands, 15 were loose tobacco packets. India is the second-largest tobacco consumer, comprises of 27.5 crore consumers which altogether greater than the population of Western Europe. From among these 27.5 crore consumers, 16.4 crore people are smokeless tobacco in takers, 6.9 crore people are exclusive smokers and 4.2 crore people are both tobacco in takers and exclusive smokers. If we take this data into consideration early mortality of 45 crore people is expected by 2050 worldwide. Female basically are prone to fewer cigarettes per day as compared to males. On the other hand, a cigarette that is consumed by females has lower nicotine content as compared to males. In developing countries, the female population has less prevalence of smoking because the level of employment is low, socio-cultural norms, and health and beauty concerns. According to the estimation by the South East Asia Region (SEAR) in the year 2000 basically from India, we encounter death of about 18% men and about 3% of women due to tobacco. Various policies have been set up to control the use of tobacco. So that threat to public health is reduced. Policies like tobacco control policy, pro-health policy are set up for this purpose. Talking about the effects on a longer-term usage of water pipe can add up to the risk of getting affected by cancers of lungs, mouth, bladders, atherosclerosis, cardiovascular and pulmonary diseases, tooth extraction, etc.

Influence of ferulic acid consumption in ameliorating the cadmium-induced liver and renal oxidative damage in rats.

The aim of this study relates to the modulatory role of ferulic acid (FA) against cadmium (Cd)-induced oxidative stress in the liver and kidney of male Wistar albino rats. Cd is an extremely toxic industrial and environmental pollutant and is well known for its varied toxic clinical manifestations. FA is a derivative of curcumin and a ubiquitous phenolic compound having a wide range of therapeutic activities. In the current study, Cd (10 mg/kg) was administered subcutaneously for 15 and 30 days to induce hepato-renal toxicity. Cd concentration was found to be significantly high in Cd-intoxicated rats (liver > kidney) while the supplementation of FA (50 mg/kg) significantly reduces the Cd concentration in liver and kidney tissues. Reduced body and organ weights and food and water consumption and increased rectal temperature were noticed in Cd-treated rats while these parameters were significantly ameliorated in FA-supplemented rats. Liver and kidney damage induced by Cd was significantly revealed by the reduction in serum total protein contents (TPC) and increased activities of serum nitric oxide (NO) levels and hepato-nephrotoxicity marker enzymes, namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), AST:ALT ratio, uric acid, urea, urea nitrogen, and creatinine, along with the increased levels of hepatic and renal oxidative stress markers, namely lipid peroxidation (MDA levels), lipid hydroperoxides (LOOH), protein carbonyl content (PCC), total oxidant status (TOS), and oxidative stress index (OSI) in liver and kidney tissues. In addition, the toxicity of Cd was also evidenced by a significant decrease in the levels of total thiols (TTH), total antioxidant concentration (TAC), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and non-enzymatic antioxidants (reduced glutathione (GSH) and total free sulfhydryl groups (TSH)). Administration of FA significantly restored the serum total protein levels and activities of serum NO levels and hepatic and renal marker enzymes to normal levels in comparison with Cd-intoxicated rats. Furthermore, FA significantly reduced the oxidative stress markers and recuperated the levels of antioxidant defense in the liver and kidney as evidenced by native PAGE and spectrophotometric assays, correlation and regression analysis and multivariate analysis of variance (MANOVA), and inferring the antioxidant role of FA. Histopathological damage due to Cd intoxication in the liver and kidney is demonstrated as vasodilatation and congestion in central veins and sinusoids as well as around the glomerulus, infiltration of mixed inflammatory cells and peripheral hemorrhage, hemorrhagic and enlarged sinusoids, disorganization of the hepatic parenchyma, focal necrosis, swelling of hepatocytes, calcified tissue inside blood vessels, hepatocyte degeneration and vacuolization of liver cells, hyaline casts, degenerated glomerulus with wide space and detached basement membrane, distal tubule with wide lumen, deformed proximal tubules with detached brush border, and degeneration and hyalinization of glomerular tuft. But, FA significantly reduced the toxicity of Cd and protected the normal histological architecture of the liver and kidney tissues. Cd-intoxicated rats were associated with a significant upregulation of TNF-α, COX-2, and HSP70 proteins, whereas treatment with FA caused downregulation of the above inflammatory markers indicating the anti-inflammatory role of FA. Principal component analysis (PCA) and Euclidean similarity measure studies clearly indicate that the liver is more prone to Cd toxicity than the kidney and FA supplementation significantly prevents oxidative stress, augmenting antioxidative status, and regaining histological parameters of the liver and kidney to normal, indicating hepato-nephroprotective, antiradical, antioxidant, and anti-inflammatory effects of this phenolic compound.

Isolation, characterization, and therapeutic activity of bergenin from marlberry (Ardisia colorata Roxb.) leaf on diabetic testicular complications in Wistar albino rats.

Bergenin is one of the phytochemical constituents in marlberry (Ardisia colorata Roxb.) having antioxidant, anti-diabetic, and anti-inflammatory properties. A. colorata has been used as an herbal medicine in Southeast Asia particularly in Northeast India to treat diabetes. Bergenin was isolated from methanol extract of A. colorata leaf (MEACL) by column chromatography and TLC profiling. Characterization and structural validation of bergenin were performed by spectroscopic analyses. A LC-ESI-MS/MS method was developed for the quantitation of bergenin and validated as per the guidelines of FDA and EMA. The validated method was successfully utilized to quantify bergenin concentration in MEACL samples. Therapeutic efficacy of bergenin was investigated on streptozotocin-induced diabetic rats by following standard protocols. Bergenin supplementation significantly improved the physiological and metabolic processes and in turn reverses diabetic testicular dysfunction via increasing serum testosterone concentrations and expression pattern of PCNA, improving histopathological and histomorphometric manifestations, modulating spermatogenic events and germ cell proliferation, restoring sperm quality, reducing sperm DNA damage, and balancing the antioxidant enzymes levels. Hence, A. colorata leaf is one of the alternate rich resources of bergenin and could be used as a therapeutic agent for diabetic testicular complications.

Testicular toxicity and sperm quality following copper exposure in Wistar albino rats: ameliorative potentials of L-carnitine.

Copper is a persistent toxic and bio-accumulative heavy metal of global concern. Continuous exposure of copper compounds of different origin is the most common form of copper poisoning and in turn adversely altering testis morphology and function and affecting sperm quality. L-carnitine has a vital role in the spermatogenesis, physiology of sperm, sperm production and quality. This study was designed to examine whether the detrimental effects of long-term copper consumption on sperm quality and testis function of Wistar albino rat could be prevented by L-carnitine therapy. The parameters included were sperm quality (concentration, viability, motility, and morphology), histopathology, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum urea, serum creatinine, serum testosterone and testis antioxidant enzyme levels (superoxide dismutase and glutathione-S-transferase), and biomarkers of oxidative stress (lipid peroxidation and expression of heat shock protein 70 in testis). Three-month-old male Wistar rats (n = 30) were divided into six groups as group 1 (G1, 0.9% saline control), group 2 (G2, CuSO4 200 mg/kg dissolved in 0.9% saline water), groups 3 and 4 (G3 and G4, L-carnitine 50 and 100 mg/kg dissolved in 0.9% saline water, respectively), and groups 5 and 6 (G5 and G6, CuSO4 200 mg/kg plus L-carnitine, 50 and 100 mg/kg dissolved in 0.9% saline water, respectively). Doses of copper (200 mg/kg) and L-carnitine (50 and 100 mg/kg) alone and in combinations along with untreated control were administered orally for 30 days. The following morphological, physiological, and biochemical alterations were observed due to chronic exposure of copper (200 mg/kg) to rats in comparison with the untreated control: (1) generation of oxidative stress through rise in testis lipid peroxidation (12.21 vs 3.5 nmol MDA equivalents/mg protein) and upregulation of heat shock protein (overexpression of HSP70 in testis), (2) liver and kidney dysfunction [elevation in serum ALT (81.65 vs 48.08 IU/L), AST (156.82 vs 88.25 IU/L), ALP (230.54 vs 148.16 IU/L), urea (12.65 vs 7.45 mmol/L), and creatinine (80.61 vs 48.25 µmol/L) levels], (3) significant decrease in body (99.64 vs 106.09 g) and organ weights (liver-3.48 vs 4.99 g; kidney-429.29 vs 474.78 mg; testes-0.58 vs 0.96 g), (4) imbalance in hormonal and antioxidant enzyme concentrations [significant decline in serum testosterone (0.778 vs 3.226 ng/mL), superoxide dismutase (3.07 vs 8.55 µmol/mg protein), and glutathione-S-transferase (59.28 vs 115.58 nmol/mg protein) levels], (5) severe alterations in the testis histomorphology [sloughed cells (90.65%, score 4 vs 15.65%, score 1), vacuolization (85.95%, score 4 vs 11.45%, score 1), cellular debris along with degenerative characteristics, accentuated germ cell depletion in the seminiferous epithelium, severe damage of spermatogonia and Sertoli cells (73.56%, score 3 vs 0%, score 1)], (6) suppression of spermatogenic process [hypospermatogenesis (low Jhonsen testicular biopsy score 4 vs 9.5), decrease in tubules size (283.75 vs 321.25 µm in diameter), and no. of germ cells (81.8 vs 148.7/100 tubules), Leydig cells (5.2 vs 36.65/100 tubules), and Sertoli cells (8.1 vs 13.5/100 tubules)], (7) sperm transit time was shorter in caput and cauda and ensued in incomplete spermatogenic process and formation of immature sperm leading to infertility, (8) sperm quality was affected significantly [decreased daily sperm production (13.21 vs 26.9 × 106 sperms/mL), sperm count (96.12 vs 154.25 × 106/g), sperm viability (26.88 vs 91.65%), and sperm motility (38.48 vs 64.36%)], and (9) increase of head (32.82 vs 2.01%) and tail (14.85 vs 0.14%) morphologic abnormalities and DNA fragmentation index (88.37 vs 11.11%). Oxidative stress and their related events appear to be a potential mechanism involved in copper testicular toxicity and L-carnitine supplementation significantly modulated the possible adverse effects of copper on seminiferous tubules damage, testes function, spermatogenesis, and sperm quality. It was validated that the use of L-carnitine at doses of 50 and 100 mg/kg protects against copper-induced testicular tissue damage and acts as a therapeutic agent for copper heavy metal toxicity.