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

Abstract

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, CuSO 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...

Bee glue (propolis) improves reproductive organs, sperm quality and histological changes and antioxidant parameters of testis tissues in rats exposed to excess copper

“…Thus, two toxic species are converted to the harmless H 2 O and . Researchers reported that accumulation excessive of Cu in the liver decreases SOD and GST activity, and causes increased MDA levels in serum and liver homogenates (Khushboo et al, ; Ozcelik & Uzun, ). Propolis administration partly cured Cu‐induced unbalance in the oxidant/antioxidant system of testis tissue.…”

“…The Cu causes to alterations in levels of LH and testosterone hormones (Chang, Choi, Kim, & Park, ), reduction the activity of 17‐beta‐hydroxysteroid dehydrogenase enzyme and damage to histoarchitecture of testicular tissues (Khushboo et al, ). Researchers reported that polyphenols of propolis have important health benefits, and they possess remarkable antioxidant effect against cell death induced by methotrexate which is a primary chemotherapeutic drug (Badr, ; Khalil, El‐Kirsh, Kamel, & El‐Rahmany, ; Wided, Hassiba, & Mesbah, ).…”

Nonenzymatically oxidized arachidonic acid regulates T‐type Ca2+ currents in mouse spermatogenic cells

“…Various groups have reported deleterious effects of spontaneous oxidation of plasma membrane phospholipids and fatty acids in mammalian spermatogenic cells and sperm. In general, phospholipids and fatty acids oxidation of mammalian spermatogenic cells induces altered testis morphology and low testicular weight, disorientation of spermatogenic cells by decreasing the diameter and epithelial thickness of seminiferous tubule, and apoptosis by an increase of caspase‐3 activity; which subsequently cause male infertility . In sperm, fatty acids oxidation produces plasma membrane damage , a reduction in antioxidant activity, spermatic abnormality, apoptosis, and DNA fragmentation .…”

“…To contend with oxidized phospholipids and fatty acids, spermatogenic cells and human sperm possess two principal protecting enzymes: superoxide dismutase and the group of glutathione peroxidase (GPX), glutathione reductase (GSH) and their substrate glutathione . In addition, human sperm also have catalases and phospholipases A2, which contribute by degrading hydroperoxylated phospholipids and fatty acids .…”

“…In addition, human sperm also have catalases and phospholipases A2, which contribute by degrading hydroperoxylated phospholipids and fatty acids . As a consequence of their biological relevance, mutations on the above mentioned enzymes or inhibition of GPX by either depletion of reductive substrate GSH by reaction with H 2 O 2 or direct inhibition of the enzyme with mercaptosuccinate, heat stress, copper or di‐n‐butyl phthalate increases the rate of spontaneous peroxidation in rat spermatogenic cells or human sperm by 20‐fold and increase infertility in humans . In addition, chemical agents like nandrolone decanoate, a synthetic anabolic steroid analog of testosterone used in pig cattle; or cyclophosphamide, a chemotherapeutic agent; both increase phospholipid peroxylation, reduce antioxidant activity, produce spermatic abnormality, apoptosis and DNA fragmentation in mammalian testicles .…”