Bee venom Apis mellifera lamarckii rescues blood brain barrier damage and neurobehavioral changes induced by methyl mercury via regulating tight junction proteins expression in rat cerebellum

Ehsan H Abu-Zeid; Bouthaina A Khalifa; Yaser H A Elewa; Ahmed H Arisha; Tamer A Ismail; Basma M Hendam; Shereen El Abdel-Hamid

doi:10.1016/j.fct.2021.112309

Bee venom Apis mellifera lamarckii rescues blood brain barrier damage and neurobehavioral changes induced by methyl mercury via regulating tight junction proteins expression in rat cerebellum

Food Chem Toxicol. 2021 Aug:154:112309. doi: 10.1016/j.fct.2021.112309. Epub 2021 May 29.

Authors

Ehsan H Abu-Zeid¹, Bouthaina A Khalifa², Yaser H A Elewa³, Ahmed H Arisha⁴, Tamer A Ismail⁵, Basma M Hendam⁶, Shereen El Abdel-Hamid⁷

Affiliations

¹ Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, 44511, Egypt. Electronic address: drehsanhashim@yahoo.com.
² Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Cairo University, Cairo, 12211, Egypt.
³ Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, 44511, Egypt; Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan. Electronic address: yaserelewa@yahoo.com.
⁴ Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Cairo, Egypt; Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.
⁵ Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
⁶ Department of Husbandry and Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
⁷ Department of Veterinary Public Health, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.

PMID: 34062221
DOI: 10.1016/j.fct.2021.112309

Abstract

The objective of the current study is to investigate the protective effect of Egyptian bee venom (BV) against methyl mercury chloride (MMC) induced blood-brain barrier (BBB) damage and neurobehavioral changes. Eighty male Sprague-Dawley rats were randomly grouped into 1^st control (C), 2^nd BV (0.5 mg/kg S/C for14 days), 3^rd MMC (6.7 mg/kg orally/14 days), and 4^th MMC + BV group. MMC exposure significantly altered rat cognitive behavior, auditory startle habituation, and swimming performance, increased the exploratory, grooming, and stereotypic behavior. MMC significantly impaired BBB integrity via induction of inflammation, oxidative stress, and down-regulation of tight junction proteins genes (TJPs) mRNA expression levels: Occludin (OCC), Claudins-5 (CLDN5), Zonula occludens-1 (ZO-1), while up-regulated the transforming growth factor-beta (TGF-β) mRNA expression levels. MMC revealed a significantly higher percentage of IgG positive area ratio, a higher index ratio of Iba1, Sox10, and ss-DNA, while index ratio of CD31, neurofilament, and pan neuron showed a significant reduction. Administration of BV significantly regulates the MMC altered behavioral responses, TJPs relative mRNA expression, and the immune-expression markers for specific neural cell types. It could be concluded for the first time that BV retains a promising in vivo protection against MMC-induced BBB dysfunction and neurobehavioral toxicity.

Keywords: Bee venom; Blood-brain barrier; Methyl mercury chloride; Neurobehavioral toxicity; Oxidative stress; Tight junction proteins.

MeSH terms

Animals
Bee Venoms / pharmacology*
Bees*
Behavior, Animal / drug effects*
Biomarkers / metabolism
Blood-Brain Barrier / drug effects*
Cerebellum / drug effects*
Cerebellum / metabolism
Male
Methylmercury Compounds / toxicity*
Oxidative Stress / drug effects
Rats
Rats, Sprague-Dawley
Tight Junction Proteins / metabolism*

Substances

Bee Venoms
Biomarkers
Methylmercury Compounds
Tight Junction Proteins