Hydrogen sulfide protects against cisplatin-induced experimental nephrotoxicity in animal models: a systematic review and meta-analysis

Abstract

Background: Cisplatin-induced acute kidney injury (cis-AKI) is not rare in oncological patients clinically, but there are limited prevention and treatment methods available. The efficacy of hydrogen sulfide (H₂S) in mitigating cis-AKI has been studied and determined in animal models.

Methods: According to the pre-registered program (PROSPERO: CRD 42023463779), we searched PubMed/Medline, Embase, and Web of Science databases using the keywords: hydrogen sulfide, cisplatin, acute kidney injury, and alternatives. A total of 13 articles met the inclusion criteria were included. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated and aggregated using random effects meta-analysis.

Results: The results showed that H₂S treatment significantly improved renal function (serum creatinine SMD = -2.96, 95% CI [-3.72 to -2.19], p < 0.00001; blood urea nitrogen SMD = -2.73, 95% CI [-3.68 to -1.78], p < 0.00001), decreased oxidative stress (superoxide dismutase SMD = 2.90, 95% CI [1.36-4.43], p = 0.0002) and inflammation levels (interleukin-1β SMD = -4.41, 95% CI [-5.84 to -2.97], p < 0.00001). However, there was a high degree of heterogeneity between studies (I² > 70%). Further subgroup analysis did not show a clear source of the heterogeneity, but various H₂S donors exhibited positive renal protection in those studies.

Conclusions: H₂S could be a new approach for treating cis-AKI, while the differential efficacies among natural and slow-release H₂S donors remain to be compared and evaluated further. This meta-analysis may shed light on establishing preclinical and clinical investigation guidelines for treating human cis-AKI with H₂S donors.

Keywords: Cisplatin-induced acute kidney injury; Experimental nephrotoxicity; Hydrogen sulfide; Vivo studies.

Figure 1. PRISMA flowchart of the search and selection process of the article.

Figure 2. Quality and risk of bias assessment.

Figure 3. Experimental cisplatin vs. H₂S forest plot showing the pooled effect of H₂S treatment on serum creatinine level.

Note: Abdel-Daim et al. (2019), Ahangarpour et al. (2014), Ahmad (2022), Cai et al. (2024), Cao et al. (2018a, , Chiarandini Fiore et al. (2008), Elkhoely & Kamel (2018), Jiang et al. (2024), Karimi et al. (2017), Sun et al. (2020), Wang, Liu & Liu (2022), Yuan et al. (2019).

Figure 4. Experimental cisplatin vs. H₂S forest plot showing the pooled effect of H₂S treatment on BUN level.

Note: Cai et al. (2024), Cao et al. (2018a, , Jiang et al. (2024), Sun et al. (2020), Wang, Liu & Liu (2022), Yuan et al. (2019).

Figure 5. Experimental cisplatin vs. H₂S forest plot showing the pooled effect of H2S treatment on SOD, MDA, GSH, IL- 1β, NF-κ B, TNF- α, and cleaved-caspase3 levels.

Note: Abdel-Daim et al. (2019), Ahangarpour et al. (2014), Ahmad (2022), Cai et al. (2024), Cao et al. (2018a, , Elkhoely & Kamel (2018), Jiang et al. (2024), Karimi et al. (2017), Sun et al. (2020), Wang, Liu & Liu (2022), Yuan et al. (2019).

Figure 6. Experimental cisplatin vs. H₂S forest plot showing the pooled effect of H₂S treatment on renal tubule injury.

Note: Ahangarpour et al. (2014), Ahmad (2022), Cai et al. (2024), Cao et al. (2018a), Chiarandini Fiore et al. (2008), Elkhoely & Kamel (2018), Jiang et al. (2024), Karimi et al. (2017), Sun et al. (2020), Wang, Liu & Liu (2022), Yuan et al. (2019).