PMID- 35227771
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 296
DP  - 2022 May 1
TI  - Vitamin E rescues valproic acid-induced testicular injury in rats: Role of 
      autophagy.
PG  - 120434
LID - S0024-3205(22)00134-5 [pii]
LID - 10.1016/j.lfs.2022.120434 [doi]
AB  - AIMS: Valproic acid (VPA), a commonly used antiepileptic drug, can induce 
      testicular oxidative stress and injury. Altered autophagic response usually 
      follows testicular injury. The study aims to evaluate the role of autophagy in 
      the protective effect of the antioxidant vitamin E (Vit E) against VPA-induced 
      testicular injury. MATERIALS AND METHODS: VPA (100, 300, and 500 mg/kg/day) was 
      administered for 8 days. The protective group received both Vit E (50 mg/kg) and 
      VPA (500 mg/kg). The testicular weight, sperm analysis, and serum testosterone 
      concentration, as well as testicular histopathology, steroidogenic gene 
      expression, and oxidative stress markers were evaluated. The mRNA or protein 
      expression of autophagy-related proteins [adenosine monophosphate-activated 
      protein kinase (AMPK), mammalian target of rapamycin (mTOR), 
      microtubule-associated protein light chain 3 (LC3), Beclin1, and p62] were 
      measured using RT-PCR or immunohistochemistry. KEY FINDINGS: VPA resulted in 
      lower testes weight and sperm quality with aberrant morphology. VPA 
      dose-dependently induced testicular oxidative stress, which was associated with 
      decreased steroidogenic gene expression and serum testosterone levels, as well as 
      deteriorated histopathology. These biochemical and histological changes were also 
      associated with autophagy induction (higher LC3 and Beclin1, and lower p62) that 
      was lost with the highest toxic dose (500 mg/kg). The attenuated autophagy with 
      the highest dose was accompanied by AMPK downregulation and mTOR upregulation. 
      Vit E protected against VPA-mediated oxidative stress and toxicity while also 
      restoring autophagic response and AMPK/mTOR levels. SIGNIFICANCE: The study 
      highlights vitamin E as a valuable protective asset against VPA-induced 
      testicular injury, possibly through AMPK-mTOR-dependent autophagy induction.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Alsemeh, Amira Ebrahim
AU  - Alsemeh AE
AD  - Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig 
      University, Egypt.
FAU - Ahmed, Marwa Mahmood
AU  - Ahmed MM
AD  - Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig 
      University, Egypt.
FAU - Fawzy, Amal
AU  - Fawzy A
AD  - Department of Biochemistry, Faculty of Medicine, Zagazig University, Egypt.
FAU - Samy, Walaa
AU  - Samy W
AD  - Department of Biochemistry, Faculty of Medicine, Zagazig University, Egypt.
FAU - Tharwat, Marwa
AU  - Tharwat M
AD  - Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig 
      University, Egypt.
FAU - Rezq, Samar
AU  - Rezq S
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig 
      University, Egypt. Electronic address: srezq@umc.edu.
LA  - eng
PT  - Journal Article
DEP - 20220225
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, rat)
RN  - 0 (LC3 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 1406-18-4 (Vitamin E)
RN  - 3XMK78S47O (Testosterone)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics
MH  - Animals
MH  - Autophagy/*drug effects/physiology
MH  - Beclin-1/metabolism
MH  - Catalase/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Microtubule-Associated Proteins/metabolism
MH  - Rats
MH  - Sperm Motility/drug effects
MH  - Superoxide Dismutase/metabolism
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Testis/*drug effects/*pathology/physiology
MH  - Testosterone/blood
MH  - Valproic Acid/*adverse effects
MH  - Vitamin E/*pharmacology
OTO - NOTNLM
OT  - Autophagy
OT  - Steroidogenesis
OT  - Testicular injury
OT  - Valproic acid
OT  - Vitamin E
EDAT- 2022/03/02 06:00
MHDA- 2022/03/23 06:00
CRDT- 2022/03/01 05:47
PHST- 2021/10/31 00:00 [received]
PHST- 2022/02/13 00:00 [revised]
PHST- 2022/02/22 00:00 [accepted]
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2022/03/01 05:47 [entrez]
AID - S0024-3205(22)00134-5 [pii]
AID - 10.1016/j.lfs.2022.120434 [doi]
PST - ppublish
SO  - Life Sci. 2022 May 1;296:120434. doi: 10.1016/j.lfs.2022.120434. Epub 2022 Feb 
      25.