Carnosine and Histidine Supplementation Blunt Lead-Induced Reproductive Toxicity through Antioxidative and Mitochondria-Dependent Mechanisms

  • Mohammad Mehdi Ommati
  • Akram Jamshidzadeh
  • Reza Heidari
  • Zilong Sun
  • Mohammad Javad Zamiri
  • Forouzan Khodaei
  • Saeed Mousapour
  • Fatemeh Ahmadi
  • Nafiseh Javanmard
  • Babak Shirazi Yeganeh


Lead (Pb)-induced reproductive toxicity is a well-characterized adverse effect associated with this heavy metal. It has been found that Pb exposure is associated with altered spermatogenesis, increased testicular degeneration, and pathological sperm alterations. On the other hand, it has been reported that Pb-induced reproductive toxicity is associated with increased reactive oxygen species (ROS) formation and diminished antioxidant capacity in the reproductive system. Hence, administration of antioxidants as protective agents might be of value against Pb-induced reproductive toxicity. This study was designed to investigate whether carnosine (CAR) and histidine (HIS) supplementation would mitigate the Pb-induced reproductive toxicity in male rats. Animals received Pb (20 mg/kg/day, oral, 14 consecutive days) alone or in combination with CAR (250 and 500 mg/kg/day, oral, 14 consecutive days) or HIS (250 and 500 mg/kg/day, oral, 14 consecutive days). Pb toxicity was evident in the reproductive system by a significant increase in tissue markers of oxidative stress along with severe histopathological changes, seminal tubule damage, tubular desquamation, low spermatogenesis index, poor sperm parameters, and impaired sperm mitochondrial function. It was found that CAR and HIS supplementation blunted the Pb-induced oxidative stress and mitochondrial dysfunction in the rat reproductive system. Thereby, antioxidative and mitochondria-protective properties serve as primary mechanisms for CAR and HIS against Pb-induced reproductive toxicity.


Heavy metals Infertility Oxidative stress Peptide Protective 


Funding information

The authors gratefully acknowledge the Pharmaceutical Sciences Research Center and the Vice Chancellor for Research, Shiraz University of Medical Sciences for the financial support (grant no. 95-01-36-11290).

Compliance with Ethical Standards

The rats were killed according to an animal protocol that was approved by the Institutional Animal Ethics Committee of Shiraz University of Medicine (Shiraz, Iran; no. 11290).

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mohammad Mehdi Ommati
    • 1
    • 2
  • Akram Jamshidzadeh
    • 1
  • Reza Heidari
    • 1
  • Zilong Sun
    • 2
  • Mohammad Javad Zamiri
    • 3
  • Forouzan Khodaei
    • 1
  • Saeed Mousapour
    • 3
  • Fatemeh Ahmadi
    • 1
  • Nafiseh Javanmard
    • 1
  • Babak Shirazi Yeganeh
    • 4
  1. 1.Pharmaceutical Sciences Research CenterShiraz University of Medical SciencesShirazIran
  2. 2.Shanxi Key Laboratory of Ecological Animal Science and Environmental MedicineAgricultural UniversityTaiguPeople’s Republic of China
  3. 3.Department of Animal Science, College of AgricultureShiraz UniversityShirazIran
  4. 4.Department of Pathology, School of MedicineShiraz University of Medical SciencesShirazIran

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