Attenuation Effect of Salvianolic Acid B on Testicular Ischemia-Reperfusion Injury in Rats

Abstract

During testicular ischemia-reperfusion, overproduction of reactive oxygen species is associated with testicular injury. We injected hydrogen peroxide (a representative of reactive oxygen species) into normal testis via the testicular artery. The experiment demonstrates that reactive oxygen species can cause spermatogenic injury. Salvianolic acid B, the most abundant bioactive component in Salvia miltiorrhiza Bunge, has been reported to possess a potent antioxidant activity. This study was conducted to evaluate the effect of salvianolic acid B on testicular ischemia-reperfusion injury in a rat testicular torsion-detorsion model. Rats were randomly separated into three groups, including 20 rats in each group: control group with sham operation, testicular ischemia-reperfusion group, and testicular ischemia-reperfusion + salvianolic acid B-treated group. In the testicular ischemia-reperfusion group, left testicular torsion of 720° for 2 hours was induced, and then testicular detorsion was carried out. Rats in the salvianolic acid B-treated group additionally had salvianolic acid B administered intravenously at detorsion. At 4 hours after detorsion, testes of 10 rats from each group were collected to analyze the protein expression of xanthine oxidase which catalyzes generation of reactive oxygen species and malondialdehyde concentration (an indirect indicator of reactive oxygen species). At 3 months after detorsion, testes of the remaining 10 rats from each group were collected to analyze spermatogenesis. Compared with the control group, xanthine oxidase protein expression and malondialdehyde concentration in ipsilateral testes of testicular ischemia-reperfusion group increased significantly, while spermatogenesis decreased significantly. In the salvianolic acid B-treated group, xanthine oxidase protein expression and malondialdehyde concentration in ipsilateral testes decreased significantly, while spermatogenesis increased significantly, compared with the testicular ischemia-reperfusion group. These results suggest that salvianolic acid B can attenuate testicular torsion/detorsion-induced ischemia/reperfusion injury by downregulating the xanthine oxidase protein expression to inhibit reactive oxygen species formation.

Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes

“…In addition, it can improve the survival rate of nude mice with fat transplantation [ 172 ]. Salvianolic acid B improves testicular spermatogenesis by reducing ROS production by downregulating the expression of xanthine oxidase in rat models of testicular torsion/detorsion-induced ischemia/reperfusion injury [ 173 ]. In rat models of crush syndrome induced via bilateral hindlimb compression using a rubber tourniquet, treatment with salvianolic acid B led to a substantial improvement in survival by alleviating kidney and cardiac dysfunction, inflammation, and endothelial dysfunction by improving mitochondrial function and exerting antibacterial effects via neutrophil extracellular traps [ 174 ].…”

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury

“…The incidence of testicular torsion is 1 in 4,000 in male individuals younger than 25 years of age, whereas the prevalence of testicular torsion out of all acute scrotal conditions is 25%–50% ( Baskovic et al, 2022 ). Despite timely detorsion, testicular atrophy may still occur in 9.1%–73.3% of patients in long-term follow up, seriously affecting their spermatogenic functions ( Wei and Huang, 2022 ). In addition, testicular atrophy, sperm quality decline, and ultimately decreased fertility were observed in an animal model of testicular torsion.…”

“…The damage caused by testicular torsion detorsion is called an ischemia-reperfusion (I/R) injury ( Chen et al, 2023 ), and I/R injuries occur after incidents of acute ischemia. Upon blood flow restoration, the testes appear to be injured by I/R, which is the primary pathophysiology of testicular torsion detorsion ( Wei and Huang, 2022 ; Almarzouq and Al, 2023 ; Alnajem and Al, 2023 ). In the I/R process, there is formation of excess reactive oxygen species (ROS), such as superoxide anions, nitric oxide, hydrogen peroxide, and hydroxyl radicals, in the affected tissue; these ROS are highly reactive and can damage the cellular constituents, such as lipids, proteins, DNA, and carbohydrates.…”

“…Once testicular torsion occurs, testicular detorsion surgery is still considered the golden method of reversing the condition, and the surgical approach is considered undeniable. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat the injuries ( Wei and Huang, 2022 ; Abdel et al, 2023 ; Chen et al, 2023 ). Therefore, the development of effective therapeutic drugs is a core problem in treating testicular I/R injuries.…”

Salvianolic Acid B Inhibits Oxidative Stress in Glomerular Mesangial Cells Alleviating Diabetic Nephropathy by Regulating SIRT3/FOXO1 Signaling

“…The most prevalent bioactive component of Salvia miltiorrhiza Bunge, known as salvianolic acid B (SAB), has been recognized in the Chinese pharmacopoeia as a distinguishing constituent of S. miltiorrhiza Bunge [14]. Numerous pharmacological effects of SAB, including antioxidation, anti-inflammation, antifibrosis, and anticancer, have been reported [15, 16]. There has been report that SAB can significantly inhibit the proliferation of human glomerular mesangial cells stimulated by high glucose, improve the intracellular redox reaction state, reduce matrix protein production and deposition, and play a positive role in the prevention and treatment of DN [17].…”