Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity

Differential regulation of COX-2/PGE2 pathway

Azza A.K. El-Sheikh, Maha Y. Kamel

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li+)-induced toxicity, GRb1 was given to rats orally (100 mg/kg) for 14 days. In independent groups, lithium chloride (4 meq/kg/day i.p.) was administered at day 4 of the experiment for 10 days, with or without GRb1. Li+ caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li+ also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control. In addition, Li caused oxidative stress in both kidney and brain, evident by significant increase in malondialdehyde and nitric oxide levels, with decrease in reduced glutathione and catalase activity. Administration of GRb1 prior to Li+ significantly improved behavioral responses, renal and brain histopathological picture, kidney function tests and oxidative stress markers compared to sole Li+-treated group. Concomitant administration of GRb1 decreased Li+ levels by about 50% in serum, urine and brain and by 35% in the kidney. Interestingly, Li+ had a differential effect on cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway, as it significantly increased COX-2 expression and PGE2 level in the kidney, while decreasing them in the brain compared to control. On the other hand, administering GRb1 with Li+ suppressed COX-2/PGE2 pathway in both kidney and brain compared to Li+ alone. In conclusion, GRb1 can alter Li+ pharmacokinetics resulting in extensively decreasing its serum and tissue concentrations. Furthermore, COX-2/PGE2 pathway has a mechanistic role in the nephro- and neuro-protective effects of GRb1 against Li+-induced toxicity.

Original languageEnglish
Pages (from-to)1873-1884
Number of pages12
JournalBiomedicine and Pharmacotherapy
Volume84
DOIs
Publication statusPublished - 1 Dec 2016

Fingerprint

Cyclooxygenase 2
Lithium
Dinoprostone
Kidney
Brain
Oxidative Stress
Kidney Function Tests
Righting Reflex
Lithium Chloride
Catalepsy
ginsenoside Rb1
Malondialdehyde
Serum
Catalase
Cerebellum
Glutathione
Nitric Oxide
Motor Activity
Pharmacokinetics
Urine

Keywords

  • Cyclooxygenase-2
  • Ginsenoside rb1
  • Lithium
  • Nephrotoxicity
  • Neurotoxicity
  • Prostaglandin E

Cite this

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title = "Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity: Differential regulation of COX-2/PGE2 pathway",
abstract = "To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li+)-induced toxicity, GRb1 was given to rats orally (100 mg/kg) for 14 days. In independent groups, lithium chloride (4 meq/kg/day i.p.) was administered at day 4 of the experiment for 10 days, with or without GRb1. Li+ caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li+ also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control. In addition, Li caused oxidative stress in both kidney and brain, evident by significant increase in malondialdehyde and nitric oxide levels, with decrease in reduced glutathione and catalase activity. Administration of GRb1 prior to Li+ significantly improved behavioral responses, renal and brain histopathological picture, kidney function tests and oxidative stress markers compared to sole Li+-treated group. Concomitant administration of GRb1 decreased Li+ levels by about 50{\%} in serum, urine and brain and by 35{\%} in the kidney. Interestingly, Li+ had a differential effect on cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway, as it significantly increased COX-2 expression and PGE2 level in the kidney, while decreasing them in the brain compared to control. On the other hand, administering GRb1 with Li+ suppressed COX-2/PGE2 pathway in both kidney and brain compared to Li+ alone. In conclusion, GRb1 can alter Li+ pharmacokinetics resulting in extensively decreasing its serum and tissue concentrations. Furthermore, COX-2/PGE2 pathway has a mechanistic role in the nephro- and neuro-protective effects of GRb1 against Li+-induced toxicity.",
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author = "El-Sheikh, {Azza A.K.} and Kamel, {Maha Y.}",
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Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity : Differential regulation of COX-2/PGE2 pathway. / El-Sheikh, Azza A.K.; Kamel, Maha Y.

In: Biomedicine and Pharmacotherapy, Vol. 84, 01.12.2016, p. 1873-1884.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Ginsenoside-Rb1 ameliorates lithium-induced nephrotoxicity and neurotoxicity

T2 - Differential regulation of COX-2/PGE2 pathway

AU - El-Sheikh, Azza A.K.

AU - Kamel, Maha Y.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li+)-induced toxicity, GRb1 was given to rats orally (100 mg/kg) for 14 days. In independent groups, lithium chloride (4 meq/kg/day i.p.) was administered at day 4 of the experiment for 10 days, with or without GRb1. Li+ caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li+ also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control. In addition, Li caused oxidative stress in both kidney and brain, evident by significant increase in malondialdehyde and nitric oxide levels, with decrease in reduced glutathione and catalase activity. Administration of GRb1 prior to Li+ significantly improved behavioral responses, renal and brain histopathological picture, kidney function tests and oxidative stress markers compared to sole Li+-treated group. Concomitant administration of GRb1 decreased Li+ levels by about 50% in serum, urine and brain and by 35% in the kidney. Interestingly, Li+ had a differential effect on cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway, as it significantly increased COX-2 expression and PGE2 level in the kidney, while decreasing them in the brain compared to control. On the other hand, administering GRb1 with Li+ suppressed COX-2/PGE2 pathway in both kidney and brain compared to Li+ alone. In conclusion, GRb1 can alter Li+ pharmacokinetics resulting in extensively decreasing its serum and tissue concentrations. Furthermore, COX-2/PGE2 pathway has a mechanistic role in the nephro- and neuro-protective effects of GRb1 against Li+-induced toxicity.

AB - To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li+)-induced toxicity, GRb1 was given to rats orally (100 mg/kg) for 14 days. In independent groups, lithium chloride (4 meq/kg/day i.p.) was administered at day 4 of the experiment for 10 days, with or without GRb1. Li+ caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li+ also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control. In addition, Li caused oxidative stress in both kidney and brain, evident by significant increase in malondialdehyde and nitric oxide levels, with decrease in reduced glutathione and catalase activity. Administration of GRb1 prior to Li+ significantly improved behavioral responses, renal and brain histopathological picture, kidney function tests and oxidative stress markers compared to sole Li+-treated group. Concomitant administration of GRb1 decreased Li+ levels by about 50% in serum, urine and brain and by 35% in the kidney. Interestingly, Li+ had a differential effect on cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway, as it significantly increased COX-2 expression and PGE2 level in the kidney, while decreasing them in the brain compared to control. On the other hand, administering GRb1 with Li+ suppressed COX-2/PGE2 pathway in both kidney and brain compared to Li+ alone. In conclusion, GRb1 can alter Li+ pharmacokinetics resulting in extensively decreasing its serum and tissue concentrations. Furthermore, COX-2/PGE2 pathway has a mechanistic role in the nephro- and neuro-protective effects of GRb1 against Li+-induced toxicity.

KW - Cyclooxygenase-2

KW - Ginsenoside rb1

KW - Lithium

KW - Nephrotoxicity

KW - Neurotoxicity

KW - Prostaglandin E

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U2 - 10.1016/j.biopha.2016.10.106

DO - 10.1016/j.biopha.2016.10.106

M3 - Article

VL - 84

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EP - 1884

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

SN - 0753-3322

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