PMID- 36047723
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20230118
IS  - 1802-9973 (Electronic)
IS  - 0862-8408 (Print)
IS  - 0862-8408 (Linking)
VI  - 71
IP  - 5
DP  - 2022 Nov 28
TI  - Rho-kinase inhibition ameliorates non-alcoholic fatty liver disease in type 2 
      diabetic rats.
PG  - 615-630
AB  - Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus 
      (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved 
      in the pathophysiology of diabetic complications. This study was designed to 
      assess the possible protective impacts of the Rho/Rho-associated coiled-coil 
      containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats 
      trying to elucidate the underlying mechanisms. Animals were assigned into control 
      rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that 
      received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric 
      measures and biochemical analyses were performed to assess metabolic and liver 
      function changes. The inflammatory and oxidative stress markers and the 
      histopathology of rat liver tissues were also investigated. Groups with T2DM 
      showed increased body weight, serum glucose, and insulin resistance. They 
      exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and 
      deterioration of liver function. Fasudil administration reduced body weight, 
      insulin resistance, and raised liver enzymes. It improved the disturbed lipid 
      profile and attenuated liver inflammation. Moreover, it slowed down the 
      progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 
      expression. The present study demonstrated beneficial amelioration effect of 
      fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving 
      dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving 
      mitochondrial architecture, and inhibiting apoptosis.
FAU - Elkattawy, H A
AU  - Elkattawy HA
AD  - Department of Basic Medical Sciences, College of Medicine, Almaarefa University, 
      Riyadh, Kingdom of Saudi Arabia. hmohammed@mcst.edu.sa.
FAU - Elsherbini, D Ma
AU  - Elsherbini DM
FAU - Ebrahim, H A
AU  - Ebrahim HA
FAU - Abdullah, D M
AU  - Abdullah DM
FAU - Al-Zahaby, S A
AU  - Al-Zahaby SA
FAU - Noser, Y
AU  - Noser Y
FAU - Hassan, A E-S
AU  - Hassan AE
LA  - eng
PT  - Journal Article
DEP - 20220831
PL  - Czech Republic
TA  - Physiol Res
JT  - Physiological research
JID - 9112413
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - Q0CH43PGXS (fasudil)
RN  - 0 (Lipids)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Non-alcoholic Fatty Liver Disease/drug therapy/pathology
MH  - rho-Associated Kinases/metabolism
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - *Insulin Resistance
MH  - *Diabetes Mellitus, Experimental/complications/drug therapy/metabolism
MH  - Liver/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Body Weight
MH  - Inflammation/metabolism
MH  - Lipids
PMC - PMC9841803
COIS- Conflict of Interest There is no conflict of interest.
EDAT- 2022/09/02 06:00
MHDA- 2022/11/30 06:00
PMCR- 2022/08/31
CRDT- 2022/09/01 08:23
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/09/01 08:23 [entrez]
PHST- 2022/08/31 00:00 [pmc-release]
AID - 934869 [pii]
AID - pr71_615 [pii]
AID - 10.33549/physiolres.934869 [doi]
PST - ppublish
SO  - Physiol Res. 2022 Nov 28;71(5):615-630. doi: 10.33549/physiolres.934869. Epub 
      2022 Aug 31.