TY - JOUR
T1 - Oxidative testicular injury
T2 - effect of l-leucine on redox, cholinergic and purinergic dysfunctions, and dysregulated metabolic pathways
AU - Erukainure, Ochuko L.
AU - Atolani, Olubunmi
AU - Banerjee, Priyanka
AU - Abel, Renata
AU - Pooe, Ofentse J.
AU - Adeyemi, Oluyomi S.
AU - Preissner, Robert
AU - Chukwuma, Chika I.
AU - Koorbanally, Neil A.
AU - Islam, Md Shahidul
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, AT part of Springer Nature.
PY - 2021/3
Y1 - 2021/3
N2 - The antioxidant and anti-proinflammatory activities of l-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed l-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO4. Treatment with l-leucine led to depletion of oxidative-induced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. l-leucine caused a significant (p < 0.05) alteration of oxidative-elevated acetylcholinesterase and chymotrypsin activities, while concomitantly elevating the activities of ATPase, ENTPDase and 5′-nucleotidase. l-leucine conferred a protective effect against oxidative induced DNA damage. Molecular docking revealed molecular interactions with COX-2, IL-1 beta and iNOS. Treatment with l-leucine led to restoration of oxidative depleted ascorbic acid-2-sulfate, with concomitant depletion of the oxidative induced metabolites: D-4-Hydroxy-2-oxoglutarate, l-cystine, adenosine triphosphate, maleylacetoacetic acid, cholesteryl ester, and 6-Hydroxy flavin adenine dinucleotide. Treatment with l-leucine reactivated glycolysis while concomitantly deactivating oxidative-induced citrate cycle and increasing the impact-fold of purine metabolism pathway. l-leucine was predicted not to be an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, with a predicted LD50 value of 5000 mg/Kg and toxicity class of 5. Additionally, l-leucine showed little or no in vitro cytotoxicity in mammalian cells. These results suggest the therapeutic potentials of l-leucine on oxidative testicular injury, as evident by its ability to attenuate oxidative stress and proinflammation, while stalling cholinergic dysfunction and modulating nucleotide hyrolysis; as well as modulate oxidative dysregulated metabolites and their pathways.
AB - The antioxidant and anti-proinflammatory activities of l-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed l-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO4. Treatment with l-leucine led to depletion of oxidative-induced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. l-leucine caused a significant (p < 0.05) alteration of oxidative-elevated acetylcholinesterase and chymotrypsin activities, while concomitantly elevating the activities of ATPase, ENTPDase and 5′-nucleotidase. l-leucine conferred a protective effect against oxidative induced DNA damage. Molecular docking revealed molecular interactions with COX-2, IL-1 beta and iNOS. Treatment with l-leucine led to restoration of oxidative depleted ascorbic acid-2-sulfate, with concomitant depletion of the oxidative induced metabolites: D-4-Hydroxy-2-oxoglutarate, l-cystine, adenosine triphosphate, maleylacetoacetic acid, cholesteryl ester, and 6-Hydroxy flavin adenine dinucleotide. Treatment with l-leucine reactivated glycolysis while concomitantly deactivating oxidative-induced citrate cycle and increasing the impact-fold of purine metabolism pathway. l-leucine was predicted not to be an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, with a predicted LD50 value of 5000 mg/Kg and toxicity class of 5. Additionally, l-leucine showed little or no in vitro cytotoxicity in mammalian cells. These results suggest the therapeutic potentials of l-leucine on oxidative testicular injury, as evident by its ability to attenuate oxidative stress and proinflammation, while stalling cholinergic dysfunction and modulating nucleotide hyrolysis; as well as modulate oxidative dysregulated metabolites and their pathways.
KW - Amino acids
KW - Antioxidants
KW - Medicinal biochemistry
KW - Proinflammation
KW - Testicular dysfunction
KW - l-leucine
UR - https://www.scopus.com/pages/publications/85101440509
U2 - 10.1007/s00726-021-02954-4
DO - 10.1007/s00726-021-02954-4
M3 - Article
C2 - 33586041
AN - SCOPUS:85101440509
SN - 0939-4451
VL - 53
SP - 359
EP - 380
JO - Amino Acids
JF - Amino Acids
IS - 3
ER -