Evaluation of the effect of administration of Tadalafil on Gentamicin-induced nephrotoxicity in rats

Mohammed, Ekhlas; Elberry, Ahmed A.; Sayed, Marwa M.; Abdelfatah, Sherif

doi:10.21608/ejmr.2022.267691

Cited by 2 publications

(4 citation statements)

References 15 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with this finding, TAD was reported to reduce both FBG and HbA1C% [ 33 ], as well as PTX did [ 34 ]. The effect of both drugs in improving kidney function was evident in the current study as indicated by the increase in Cr Cl & the decrease in S. Cr which is in line with other studies [ 35 – 37 ].…”

Section: Discussionsupporting

confidence: 92%

Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial

Hegazy,

Amaar,

Hegab

2024

Diabetol Metab Syndr

View full text Add to dashboard Cite

Aims To investigate the efficacy and safety of tadalafil (TAD) versus pentoxifylline (PTX) in the management of diabetic kidney disease (DKD). Some animal studies and clinical trials reported that tadalafil and pentoxifylline have a reducing effect on different blood glucose parameters and lipid profiles which contribute to progress the patients with diabetes mellitus (DM) to DKD. Methods From February 2022 to March 2023, 90 patients with type 2 DM and DKD (micro-albuminuria) were enrolled in this randomized-controlled study. The patients were randomized into three equal groups: control group, TAD group, and PTX group. The three groups received traditional blood glucose lowering therapy + ramipril 10 mg PO. The TAD group also received tadalafil 20 mg PO every other day. The PTX group also received pentoxifylline 400 mg PO twice daily. Results Both TAD and PTX groups produced statistically significant improvement in the primary outcomes by a significant reduction in Urinary albumin/creatinine ratio (UACR) which was pronounced by a reduction percentage of—47.47%, −53.73% respectively. In addition to a significant decrease in Hemoglobin A1C (HbA1c) (mmol/mol), Fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PPG) (p < 0.001). Only the PTX group showed a significant increase in Cr Cl and a significant decrease in S. Cr (p < 0.001). Only the TAD group showed a significant increase in high-density lipoprotein—cholesterol (HDL-C) (p < 0.001), while the PTX group showed a significant decrease in low-density lipoprotein—cholesterol (LDL-C) (p-value 0.011), and triglyceride (p-value 0.002). Both TAD and PTX groups showed a decrease in tumor necrosis factor-α (TNF-α) which was significant only in the PTX group (p < 0.001). There was a significant increase in malondialdehyde (MDA) (p < 0.001), and an increase in urinary neutrophil gelatinase-associated Lipocalin (uNGAL) (p-value 0.850, 0.014 respectively) which was significant only in the PTX group. Conclusions The use of tadalafil or pentoxifylline may serve as an effective adjuvant therapy for patients with diabetic kidney disease. Trial Registration: ClinicalTrials.gov identifier NCT05487755, July 25, 2022.

show abstract

Section: Discussionsupporting

confidence: 92%

Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial

Hegazy,

Amaar,

Hegab

2024

Diabetol Metab Syndr

View full text Add to dashboard Cite

show abstract

“…In our study, the group treated with TAD along with AmB showed reduced renal NO content, down-regulated iNOS, and up-regulated eNOS protein expression by comparison to AmB group. Parallel to our results, a previous study has demonstrated the protective of TAD agaist gentamicin-induced nephrotoxicity by regulating renal NO content and iNOS/eNOS expression (Mohammed et al, 2022 ). These regulatory effects of TAD could be partly attributed to its anti-inflammatory and antioxidant properties that attenuate NF-κB/iNOS signaling.…”

Section: Discussionsupporting

confidence: 90%

“…In our study, pretreatment with TAD showed remarkable attenuation of oxidative damage in AmB-treated rats where renal MDA content was reduced while GSH content was elevated. These results are parallel to those of previous studies elucidating the nephroprotective effect of TAD against contrast-induced nephropathy, diabetic nephropathy, gentamicin-, and cisplatin-induced nephrotoxicity models via its antioxidant properties (Adeneye and Benebo, 2016 , Elhawary and Abd Allah, 2017 , Iordache et al, 2020 , Mohammed et al, 2022 ).…”

Section: Discussionsupporting

confidence: 88%

“…In addition, the regulatory effects of TAD on NO production through iNOS and endothelial NOS (eNOS) enzymes have been reported to participate in attenuation of inflammatory signaling and cytokine production (Azouz et al, 2020 ). Interestingly, the protective effects of TAD against renal ischemia/reperfusion injury, cisplatin, and gentamicin nephrotoxicity have been elucidated by different studies (Adeneye and Benebo, 2016 , Maruyama et al, 2022 , Mohammed et al, 2022 ). Therefore, we designed our study to investigate for the first time the possible underlying defensive mechanism of TAD against AmB-induced AKI in rats.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B–induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling

Abdel-Rahman,

Messiha,

Ali

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Amphotericin B (AmB)–induced acute kidney injury (AKI) is a common health problem having an undesirable impact on its urgent therapeutic utility for fatal systemic fungal infections. Tadalafil (TAD), a phosphodiesterase-5 (PDE-5) inhibitor, has been observed to have a wide range of pharmacological actions, including nephroprotection. The study’s objective was to examine the possible underlying protective mechanism of TAD against AmB-induced nephrotoxicity. Experimentally, animals were divided randomly into four groups: control, TAD (5 mg/kg/day; p.o.), AmB (18.5 mg/kg/day; i.p.), and TAD+AmB groups. Sera and tissue samples were processed for biochemical, molecular, and histological analyses. The biochemical investigations showed that TAD significantly ameliorated the increase of kidney function biomarkers (creatinine, urea, CysC, KIM-1) in serum, renal nitric oxide (NO), lipid peroxidation (MDA), and inflammatory cytokines (TNF-α, IL-6) in AmB-treated rats. Meanwhile, TAD significantly retarded AmB-induced decrease in serum magnesium, sodium, potassium, and renal glutathione content. Molecular analysis revealed that TAD reduced AmB-induced imbalance in the protein expression of eNOS/iNOS, which explains its regulatory effect on renal NO content. These results were also supported by the down-regulation of nuclear NF-κB p65 and cleaved caspase-3 protein expressions, as well as the improvement of histological features by TAD in AmB-treated rats. Therefore, it can be suggested that TAD could be a promising candidate for renoprotection against AmB-induced AKI. That could be partly attributed to its regulatory effect on renal eNOS/iNOS balance and NO, the inhibition of NF-κB p65 nuclear translocation, its downstream inflammatory cytokines and iNOS, and ultimately the inhibition of caspase-3-induced renal apoptosis.

show abstract

Evaluation of the effect of administration of Tadalafil on Gentamicin-induced nephrotoxicity in rats

Cited by 2 publications

References 15 publications

Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial

Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial

Regulation of renal nitric oxide and eNOS/iNOS expression by tadalafil participates in the mitigation of amphotericin B–induced renal injury: Down-regulation of NF-κB/iNOS/caspase-3 signaling

Contact Info

Product

Resources

About