A Histopathological, Immunohistochemical and Biochemical Investigation on the in vitro Antioxidant, Myeloprotective, Hematoprotective and Hepatoprotective Effects of Hypericum triquetrifolium Seed Extract Against Cyclophosphamide-Induced Toxicity

Abstract

The aim of this study was to investigate in vitro antioxidant properties and in vivo protective effects of the methanol extract of the Hypericum triquetrifolium Turra (HT) seed against acute hepatotoxicity, myelotoxicity and hematotoxicity in rats induced by cyclophosphamide (CP). In order to investigate in vivo protective effects of the HT extract on rat tissues, the rats were divided into nine groups. The toxic effects of CP and the protective effects of HT extract on nucleated cells that are produced by bone marrow, serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and oxidative stress index (OSI) levels were investigated biochemically. Additionally, liver tissue samples were examined for histopathological changes and apoptosis by Bcl-2, Bax and caspase-3 immunohistochemistry. The results of this study show that HT seed methanol extract has high total phenolic content (179.52 μg GAE/mg) and antioxidant activity (87.48% in 500 μg/mL concentration). CP administration caused hepatotoxicity, myelotoxicity and hematotoxicity in the rats. Whereas, the groups of rats that were injected with different concentrations of HT (25, 50 and 100 mg/kg) and CP (150 mg/kg) showed significant protective effects on bone marrow nucleated cells and important decreases on serum ALT, ALP, LDH and OSI levels were observed when compared with the CP injected group.

Myeloprotective and hematoprotective role of kefir on cyclophosphamide toxicity in rats

“…In the present study, the bone marrow nucleated cell level demonstrated a statistically significant decrease in the group that was administered CPx compared to the control value. In a similar study, it was reported that CPx reduced bone marrow nucleated cell levels and caused myelotoxicity [26,40]. It was reported in a previous studies that CPx-induced myelosuppression / immunotoxicity limited the use of CPx [41,42].…”

“…CPx, which has been known to be effective in the treatment of cancer and non-malignant diseases since 1958 and has a wide area of use in many neoplastic diseases as a standalone drug or in combination with other chemotherapeutics, also includes side-effects [25]. The fact that CPx causes multi-organ damage limits the effective high-dose use of the drug [26]. Hematopoietic depression is among the main side-effects of CPx.…”

Investigation of uroprotective effects of seed methanol extracts of Hypericum triquetrifolium Turra. on cyclophosphamide-induced bladder hemorrhagic cystitis and nephrotoxicity in Wistar albino rats

“…The aerial parts of HT with methanolic extract possesses high antioxidant activities 23 which might be useful in protecting against or decelerating the development of diverse oxidative stress-induced disorders 24 . Thus, HT is a strong candidate to protect the healthy cells from the toxic side effects of CYP 25 .…”

Therapeutic and protective role of curcumin nanoparticles against experimentally induced hepatotoxicity in rats

“…(Matalon et al, 2004;Altaylý et al, 2012). CP, an alkylating chemotherapeutic drug, is metabolized by liver cytochrome P450 enzymes, namely CYP3A4 and CYP2B6 which demonstrate active therapeutic and cytotoxic metabolites and diffuse out of the hepatocytes into the plasma (Yildiz, et al, 2019). CP spreads throughout the body and generates two active metabolites: phosphoramide mustard (PAM) and acrolein (ACR).…”

“…Thus, it interacts with protein and causes changes in the structure and function of enzymes and harms the tissue antioxidant defense mechanism. CPinduced toxicity is a consequence of a mitochondrial dysfunction and ends with a decrease of adenosine triphosphate owing to nitrosative and oxidative stress (Yildiz, et al, 2019). Curcumin's biological activity is attributed to its bioavailability in humans.…”