PMID- 38137521
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231225
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 12
DP  - 2023 Dec 13
TI  - The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in 
      Streptozocin-Induced Diabetic Rats.
LID - 10.3390/biomedicines11123300 [doi]
LID - 3300
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease due 
      to insulin resistance. Oxidative stress complicates the etiology of T2DM. 
      Saxagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, while 
      Pioglitazone is a thiazolidinedione insulin sensitizer. This study aimed to 
      assess the effect of Saxagliptin and Pioglitazone monotherapy and combination 
      therapy on the biochemical and biological parameters in streptozotocin 
      (STZ)-induced diabetic rats. METHODS: The study included thirty-five male albino 
      rats. Diabetes mellitus was induced by intraperitoneal STZ injection (35 mg/kg). 
      For a 1-month duration, rats were divided into five groups. Glucose homeostasis 
      traits, lipid profiles, kidney functions, liver enzymes, and oxidative stress 
      markers were measured. Gene expression of miRNA-29a, phosphoenolpyruvate 
      carboxykinase (PEPCK), phosphoinositide-3-kinase (PI3K), and interleukin 1 beta 
      (IL-1beta) was assessed using qRT-PCR. RESULTS: At a 1-month treatment duration, 
      combination therapy improves oxidative stress markers more than either drug 
      alone. The combination therapy had significantly higher levels of SOD, catalase, 
      and GSH and lower levels of MDA compared to the monotherapy. Additionally, the 
      diabetic group showed a significant increase in the expression levels of 
      miRNA-29a, PEPCK, and IL-1beta and a significant decrease in PI3K compared to the 
      normal control group. However, combination therapy of Saxagliptin and 
      Pioglitazone was more effective than either Saxagliptin or Pioglitazone alone in 
      reversing these results, especially for PEPCK and IL-1beta. CONCLUSIONS: Our 
      findings revealed that combining Saxagliptin and Pioglitazone improves glycemic 
      control and genetic and epigenetic expression profiles, which play an essential 
      regulatory role in normal metabolism.
FAU - Othman, Ahmed Mohamed
AU  - Othman AM
AUID- ORCID: 0000-0003-1264-9678
AD  - Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 
      41522, Egypt.
FAU - Ashour Ibrahim, Ibrahim
AU  - Ashour Ibrahim I
AD  - Department of Biochemistry, Faculty of Veterinary Medicine, Suez Canal 
      University, Ismailia 41522, Egypt.
FAU - Saleh, Samy M
AU  - Saleh SM
AD  - Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 
      41522, Egypt.
FAU - Abo-Elmatty, Dina M
AU  - Abo-Elmatty DM
AD  - Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 
      41522, Egypt.
FAU - Mesbah, Noha M
AU  - Mesbah NM
AUID- ORCID: 0000-0002-8863-968X
AD  - Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 
      41522, Egypt.
FAU - Abdel-Hamed, Asmaa R
AU  - Abdel-Hamed AR
AUID- ORCID: 0000-0003-2951-6046
AD  - Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 
      41522, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20231213
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10741989
OTO - NOTNLM
OT  - Pioglitazone
OT  - Saxagliptin
OT  - diabetes mellitus
OT  - miRNA-29a
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2023/12/23 12:44
MHDA- 2023/12/23 12:45
PMCR- 2023/12/13
CRDT- 2023/12/23 01:10
PHST- 2023/11/03 00:00 [received]
PHST- 2023/11/26 00:00 [revised]
PHST- 2023/11/29 00:00 [accepted]
PHST- 2023/12/23 12:45 [medline]
PHST- 2023/12/23 12:44 [pubmed]
PHST- 2023/12/23 01:10 [entrez]
PHST- 2023/12/13 00:00 [pmc-release]
AID - biomedicines11123300 [pii]
AID - biomedicines-11-03300 [pii]
AID - 10.3390/biomedicines11123300 [doi]
PST - epublish
SO  - Biomedicines. 2023 Dec 13;11(12):3300. doi: 10.3390/biomedicines11123300.