Therapy of the rat hemorrhagic cystitis induced by cyclophosphamide. Stable gastric pentadecapeptide BPC 157, L-arginine, L-NAME

Sučić, Mario; Luetić, Krešimir; Jandrić, Ivan; Drmic, Domagoj; Sever, Anita Zenko; Vuletić, Lovorka Batelja; Halle, Željka Belošić; Strinic, Dean; Kokot, Antonio; Seiwerth, Ranka Serventi; Zoricic, Ivan; Blagaić, Alenka Boban; Seiwerth, Sven; Sikirić, Predrag

doi:10.1016/j.ejphar.2019.172593

Cited by 38 publications

(70 citation statements)

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“…CPX-induced changes in urogenital tract in animals are well described in various experimental models of CPX toxicity. The model of single intraperitoneal injection of CPX in a dose of 200 mg/kg is often used with the studied compound administered before or after the CPX injection to induce acute hemorrhagic cystitis or testicular toxicity [10,23,24], but other regimens of CPX administration are also applied, e.g., daily intraperitoneal injection of 100 mg/kg CPX dose for 3 days [25]. We chose 10 days intragastric administration of CPX in a low daily dose of 15 mg/kg with concomitant administration of NaMSA (100 mg/kg) as the potentially protective agent.…”

Section: Discussionmentioning

confidence: 99%

Morin-5′-Sulfonic Acid Sodium Salt (NaMSA) Attenuates Cyclophosphamide-Induced Histological Changes in Genitourinary Tract in Rats—Short Report

et al. 2021

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Cyclophosphamide (CPX) exerts toxicity in the urogenital system. The current study was designed to evaluate the effect of morin-5′-sulfonic acid sodium salt (NaMSA) on CPX-induced urogenital toxicity in rats. NaMSA (100 mg/kg/daily) and CPX (15 mg/kg/daily) alone or in combination and 0.9% NaCl (as a control) were given intragastrically for 10 days. Testes and epididymes from male and urinary bladders from male and female rats were evaluated histologically. In testes and epididymes, morphological changes and relative decrease in sperm count were assessed. In urinary bladders edema, hemorrhage and urothelium erosions were described by 0–2 points scoring system. Reproductive score (RS—in total 6 points) and urinary bladder score (BS—in total 6 points) were thereafter calculated. In CPX-receiving group RS (2.7) and BS (3.3) were significantly higher than in the control (0.5 and 0.25 for RS and BS, respectively). Co-administration of NaMSA reversed most of the morphological changes, which was reflected by lower RS and BS score (0.5 and 1.2 for RS and BS, respectively). The preliminary findings suggest that NaMSA may attenuate CPX-induced histological changes in rat urogenital tract.

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Section: Discussionmentioning

confidence: 99%

Morin-5′-Sulfonic Acid Sodium Salt (NaMSA) Attenuates Cyclophosphamide-Induced Histological Changes in Genitourinary Tract in Rats—Short Report

et al. 2021

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“…It plays an important role in regulating the body’s water, salt, and ion balance [ 1 , 2 ]. Cyclophosphamide (CTX) is widely used as an anticancer drug [ 3 , 4 ], although it can cause side effects such as cardiotoxicity, nephrotoxicity, and hepatotoxicity. The process of CTX-induced renal pathological damage includes apoptosis and necrosis of renal tubular epithelial cells [ 5 ], release of inflammatory factors, and mediation of inflammatory response [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Ameliorating Effect of Pentadecapeptide Derived from Cyclina sinensis on Cyclophosphamide-Induced Nephrotoxicity

et al. 2020

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Cyclophosphamide (CTX) is a widely used anticancer drug with severe nephrotoxicity. The pentadecapeptide (RVAPEEHPVEGRYLV) from Cyclina sinensis (SCSP) has been shown to affect immunity and to protect the liver. Hence, the purpose of this study was to investigate the ameliorating effect of SCSP on CTX-induced nephrotoxicity in mice. We injected male ICR mice with CTX (80 mg/kg·day) and measured the nephrotoxicity indices, levels of antioxidant enzymes, malondialdehyde (MDA), inflammatory factors, as well as the major proteins of the NF-κB and apoptotic pathways. Cyclophosphamide induced kidney injury; the levels of kidney-injury indicators and cytokines recovered remarkably in mice after receiving SCSP. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) increased, while there was a significant decrease in MDA levels. The kidney tissue damage induced by CTX was also repaired to a certain extent. In addition, SCSP significantly inhibited inflammatory factors and apoptosis by regulating the NF-κB and apoptotic pathways. Our study shows that SCSP has the potential to ameliorate CTX-induced nephrotoxicity and may be used as a therapeutic adjuvant to ameliorate CTX-induced nephrotoxicity.

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“…BPC 157 has also been found to counteract both vein hypertension and arterial hypotension in rat interior vein ligature model 33 . The modulatory effect of BPC 157 on balancing the nitric oxide-related system including counteracting L-NAME-hypertension as well as L-arginine-hypotension in different animal studies have been largely reported 2,7,8,34 . In this study, although we proved that ex vivo nitric oxide-and endothelium-related vasodilation in normal large vessel was induced only by BPC 157 at high concentration, it could not be ruled out that BPC 157 at low concentration might counteract the imbalanced blood pressure under an in vivo diseased condition through a currently unknown mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Since the first demonstration of nitric oxide generation in gastric mucosa which contributed to the antiulcer effect of BPC 157 in gastric lesion assay by Sikiric et al 5 , following studies analyzing the influence by treating together or alone with nitric oxide inhibitor, N ω -nitro-l-arginine methyl ester (L-NAME) or nitric oxide precursor, L-arginine all showed that the nitric oxide modulation is involved in the healing effect of BPC 157 in different tissue injuries. A considerable number of evidences provided by Sikiric et al further demonstrated the modulatory role of BPC 157 on nitric oxide generation 7 – 11 . Our previous study reveals that BPC 157 can markedly promote the expression of vascular endothelial growth factor VEGF receptor 2 (VEGFR2) and angiogenesis in ischemic hind limb 6 .…”

Section: Introductionmentioning

confidence: 99%

Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway

Hsieh

Lee

Chueh

et al. 2020

Sci Rep

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BPC 157-activated endothelial nitric oxide synthase (eNOS) is associated with tissue repair and angiogenesis as reported in previous studies. However, how BPC 157 regulates the vasomotor tone and intracellular Src-Caveolin-1 (Cav-1)-eNOS signaling is not yet clear. The present study demonstrated a concentration-dependent vasodilation effect of BPC 157 in isolated rat aorta. Attenuation of this vasodilation effect in the absence of endothelium suggested an endothelium-dependent vasodilation effect of BPC 157. Although slightly increased vasorelaxation in aorta without endothelium was noticed at high concentration of BPC 157, there was no direct relaxation effect on three-dimensional model made of vascular smooth muscle cells. The vasodilation effect of BPC 157 was nitric oxide mediated because the addition of L-NAME or hemoglobin inhibited the vasodilation of aorta. Nitric oxide generation was induced by BPC 157 as detected by intracellular DFA-FM DA labeling which was capable of promoting the migration of vascular endothelial cells. BPC 157 enhanced the phosphorylation of Src, Cav-1 and eNOS which was abolished by pretreatment with Src inhibitor, confirming the upstream role of Src in this signal pathway. Activation of eNOS required the released binding with Cav-1 in advance. Co-immunoprecipitation analysis revealed that BPC 157 could reduce the binding between Cav-1 and eNOS. Together, the present study demonstrates that BPC 157 can modulate the vasomotor tone of an isolated aorta in a concentration- and nitric oxide-dependent manner. BPC 157 can induce nitric oxide generation likely through the activation of Src-Cav-1-eNOS pathway.

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Therapy of the rat hemorrhagic cystitis induced by cyclophosphamide. Stable gastric pentadecapeptide BPC 157, L-arginine, L-NAME

Cited by 38 publications

References 50 publications

Morin-5′-Sulfonic Acid Sodium Salt (NaMSA) Attenuates Cyclophosphamide-Induced Histological Changes in Genitourinary Tract in Rats—Short Report

Morin-5′-Sulfonic Acid Sodium Salt (NaMSA) Attenuates Cyclophosphamide-Induced Histological Changes in Genitourinary Tract in Rats—Short Report

Ameliorating Effect of Pentadecapeptide Derived from Cyclina sinensis on Cyclophosphamide-Induced Nephrotoxicity

Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway

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