The chemotherapeutic and immunosuppressive agent cyclophosphamide has previously been shown to induce complications within the setting of bone marrow transplantation. More recently, cardiotoxicity has been shown to be a dose-limiting factor during cyclophosphamide therapy, and cardiooncology is getting wider attention. Though mechanism of cyclophosphamide-induced cardiotoxicity is not completely understood, it is thought to encompass oxidative and nitrative stress. As such, this review focuses on antioxidants and their role in preventing or ameliorating cyclophosphamide-induced cardiotoxicity. It will give special emphasis to the cardioprotective effects of natural, plant-derived antioxidants that have garnered significant interest in recent times.

Background Globally, cardiovascular diseases (CVDs) are becoming the major cause of death. Urtica simensis is one of endogenous plant which treats a wide range of disease conditions including heart diseases. However, there is limited information on safety and efficacy of the plant. Objective To evaluate the in vitro antioxidant, the in vivo cardioprotective activity of crude extract and solvent fractions of Urtica simensis leaves on cyclophosphamide-induced myocardial injury. Methods The cardioprotective activity of the crude extract, aqueous and hexane fraction of Urtica simensis leaves was evaluated based on anatomical, biochemical and histopathological methods. The in vitro antioxidant activity of the plant was also assayed in terms of free radical scavenging activity (RSA). Results Crude extract and solvent fractions of Urtica simensis significantly prevented the deleterious effect of cyclophosphamide on body weight (P<0.001), heart weight to body ratio (P<0.01), cardiac biomarkers including troponin I (P<0.01), alanine transaminase (ALT) (P<0.001), aspartate aminotransferase (AST) (P<0.01) and lipid profiles including triglycerides (P<0.001) and total cholesterol (P<0.01). The histopathological study confirmed presence of necrosis, oedema and haemorrhage on cyclophosphamide alone-treated groups while the 200mg/kg and 400mg/kg of the crude extract and aqueous fraction showed normal cardiocytes. The antioxidant assay of Urtica simensis plant exhibited free radical scavenging activity of inhibitory concentration of 50% (IC 50 ) for the crude extract with the values of 63.27µg/mL, aqueous fraction with the values of 136.38µg/mL and hexane fraction with the values of 258.70µg/mL. Conclusion Crude extract and solvent fractions of Urtica simensis leaves have cardioprotective activities. The cardioprotective effect could be attributed to the antioxidant activity of the plant extracts. However, this requires further in-depth understanding.

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Cyclophosphamide is an alkylating antineoplastic agent, and it is one of the most successful drugs with wide arrays of clinical activity. It has been in use for several types of cancer treatments and as an immunosuppressive agent for the management of autoimmune and immune-mediated diseases. Nowadays, its clinical use is limited due to various toxicities, including nephrotoxicity. Even though the mechanisms are not well understood, cyclophosphamide-induced nephrotoxicity is reported to be mediated through oxidative stress. This review focuses on the potential role of natural and plant-derived antioxidants in preventing cyclophosphamide-induced nephrotoxicity.

Telmisartan is an angiotensin II receptor antagonist, which selectively inhibits the angiotensin II type 1 receptor. Thus, it is widely used for hypertension management. Nowadays, telmisartan's effect on peroxisome proliferator-activated receptors (PPARs) is gaining wider attention. PPARs are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Telmisartan is reported to have a partial PPARγ-agonistic effect while avoiding the safety concerns found with full PPARγ agonists (thiazolidinediones). Telmisartan could be an alternative treatment option, with dual benefit for diabetes mellitus (DM) and hypertension. This review summarizes the anti-diabetic activity of telmisartan via its partial PPARγ-agonistic activity.

Background: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED. Methods: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics. Results: A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failureinduced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and agerelated ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase. Conclusion: Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.

Diabetic retinopathy (DR) is a retinal vascular disorder associated with both type 1 and type 2 diabetes mellitus (DM). It is characterized by specific loss of pericytes, which leads to an augmented blood vessel permeability, and development of new blood vessels (retinal neovascularization). Moreover, stiffening of eye membrane, inflammation, and apoptosis of endothelial cells also lead to damage of the blood-retinal barrier and blindness in most cases unless it's detected and managed early. Hence, this review was intended to assess the potential roles of Netrin-1 and-4 as new/alternative biomarkers and therapeutic options for DR. Netrin-1 and-4 have been the most known ligands and are well known for their role in neural guidance. DR has both neural and vascular components; therefore, biomarkers used for both neural and vascular retinal tissues are potentially important. According to different experimental and clinical studies, as compared to the normal groups, there was a significant increment in both retinal Netrin-1 and-4 mRNA and protein levels in the retinopathy groups. In addition, exogenous supplementation of these proteins is also used as a therapeutic agent for DR.

Leishmaniasis is a widespread group of neglected parasitic diseases caused by protozoa of the genus Leishmania. Around 2 million new cases are reported each year and around 12 million people are at risk of being infected. Although various therapies have been used to treat leishmaniasis, they have been associated with increased cytotoxicity and drug resistance problems. Hence, the present review was intended to show the potential of tamoxifen as an alternative option for the treatment of leishmaniasis. Tamoxifen is a known selective estrogen receptor modulator and has been widely used for the treatment of early-stage breast cancer. Various experimental and clinical studies revealed that it has an antileishmanial effect by decreasing parasitic burden, with low cost and few side effects. The antileishmanial action of tamoxifen has been related to its potential effect on sphingolipid metabolism. Besides, it affects mitochondrial function by inducing alterations in the plasma membrane potential. However, further detailed studies are required to show the ultimate effects on health outcomes.