Linagliptin, the dipeptidyl peptidase‐4 enzyme inhibitor, lessens CHOP and GRP78 biomarkers levels in cisplatin‐induced neurobehavioral deficits: A possible restorative gateway

Abstract

Cisplatin (CP) is a cornerstone chemotherapeutic agent, however, its neurotoxicity is a chief cause of its limited usage. Linagliptin, which is a dipeptidyl peptidase‐4 enzyme inhibitor, has exhibited considerable neuroprotective potential. We aimed to evaluate the linagliptin modulatory effects on endoplasmic reticulum (ER) stress, redox status, and apoptosis in CP‐induced neurotoxicity. Thirty mice were allocated equally into the control group, Group II: CP group, and Group III: linagliptin treated CP group. All groups were subjected to the measurement of hippocampal messenger RNA gene expression of glucose‐regulated protein‐78 and C/EBP homologous protein (CHOP). Peroxisome proliferator‐activated receptor γ coactivator 1α and cleaved caspase‐3 levels were assessed by the enzyme‐linked immunosorbent assay technique while malondialdehyde, reduced glutathione levels and superoxide dismutase activity were detected spectrophotometrically. Linagliptin ameliorated ER stress and enhanced antioxidant status with cognitive function improvement. Linagliptin may be considered a promising neuroprotective agent owing to its ability to reduce ER/oxidative stress.

Beneficial effects of linagliptin in cell culture model of Parkinson’s disease

“…We found that LNG down-regulated caspase-3 expression and showed antiapoptotic effects, confirming previous studies. Previously it has been reported that LNG has a marked neuroprotective, anti-apoptotic and cognitive improving properties in in-vitro cerebral ischemia model [27].…”

Brain Protection by Methylene Blue and Its Derivative, Azur B, via Activation of the Nrf2/ARE Pathway in Cisplatin-Induced Cognitive Impairment

“…Several cytotoxic compounds including cisplatin may facilitate impairment of LTP. Cisplatin-induced cognitive impairment was documented in animals models using Morris water maze [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], Y-maze test [ 33 , 41 , 42 , 43 , 44 ], T-maze [ 45 , 46 , 47 ], and novel object recognition test [ 9 , 48 , 49 , 50 , 51 ], including in humans in the treatment of oncological diseases using chemotherapy using cisplatin as a chemostatic [ 12 , 52 , 53 , 54 , 55 ].…”

Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity

“…Cisplatin (CDDP) is one of the leading anticancer agents in cancer chemotherapy. The consistent worry of clinicians about cisplatin use is the variegated side effects chiefly linked with neurotoxicity, nephrotoxicity, and testicular 7,23,24 However, studies probing into the mechanisms of CDDP toxicity show that a network of oxidative stress, pro-inflammation and redox-mediated apoptosis play a pivotal role. 25 Emerging research reports have revealed increasing interest for exploration of natural products to combat the integrated mechanism underlying the severe side effects of CDDP.…”

“… 29 , 31 Cisplatin is clinically known to cause structural CNS mutilations which correlate with the cognitive deficits observed in CDDP‐treated patient. 23 Therefore, our study examined CICI and behavior of rats after CDDP injection via MWM and Y maze tests. Morris water-maze test is a very common behavioral model to test rodent spatial memory and learning.…”

“…Our findings regarding the aforementioned redox indices agreed with earlier reports on the oxidative effect of CDDP on the brain, kidney, and testis. 7,23,39,42,43 It was interesting to observe that TT co-administration mitigated MDA release and significantly restored brain antioxidant defences dose dependently. Therefore, the beneficial health effect of TT in the current study demonstrates its antioxidant property and also support the reported action of TT in previous studies.…”