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Hepatocellular carcinoma (HCC) is one of the most common malignancies and it is the fourth cause of cancer-related mortality. The treatment of HCC with traditional chemotherapeutic agents such as doxorubicin has been limited due to poor efficacy, acquired resistance of the tumors and systemic toxicity. Verapamil as a P-gp inhibitor has demonstrated anti-cancer activities both in vitro and in vivo. Natural products and plant-derived compounds, such as ginger extract, have been investigated as safe and effective anti-cancer agents. Combination therapy offers preferable prognosis with less side effects. For example, the combination of chemotherapeutics with verapamil or ginger extract has been shown to exert beneficial therapeutic effects, overcome multidrug resistance and reduce side effects through modulation of different signaling pathways in tumor cells. Nano-sized formulations are designed to increase accumulation of drugs at the tumor environment and to improve solubility/bioavailability, promote retention, specificity, efficacy and safety. This review summarizes how to overcome cardiotoxicity and multidrug resistance evolved by doxorubicin in HCC treatment.

Osteoarthritis [OA] is a chronic, prevalent, debilitating joint disease characterized by progressive cartilage degradation, subchondral bone remodeling, bone marrow lesions, meniscal damage, and synovitis. Joint diseases are very difficult to be treated with traditional line therapy. Hence the importance of developing new therapeutic methods such as stem cell therapy. Mesenchymal Stem Cells [MSCs] isolated from multiple tissues as bone marrow, adipose tissue, dental pulp, placenta and umbilical cord. They possess ability of self-renewal and multilineage differentiation which is a hoping tool for treatment of multiple diseases. The aim of this study is to assess the ability of stem cells to differentiate into chondrocytes and the ability of those chondrocytes to induce cartilage repair and suppresses cartilage degeneration in Monosodium iodoacetate [MIA] induced osteoarthritis in rats' model. In this experimental study Wharton jelly separated from umbilical cord was used to isolate MSCs then differentiated to chondrocytes and injected into MIA induced osteoarthritis in rat's model. The rats divided into three groups; control group, MIA-treated group and MIA- Chondrocytes treated group. Results: MIA- Chondrocytes treated group appeared healthy with no signs of inflammation. On microscopic examination: the articular cartilage of injected limbs showed observable restoration of surface continuity, chondrocytes density, boundaries between layers and matrix basophilia. Conclusion: Intra-articular injection of chondrocytes improves, inhibits the progression of degeneration of the affected cartilage and induces cartilage repair.

Background: Management of acute kidney injury is still facing a big problem. It is only dependent up till now on supportive measures, like fluid resuscitation and renal replacement therapy. No current drug therapy has been approved for the treatment of acute kidney injury. Acute kidney injury situations in a lot of cases can be predicted so, finding a drug for AKI will really benefit many patients. The pathophysiology of AKI is complex and many signaling pathways are involved in it. The Glycogen synthase kinase 3B enzyme is an important member in some of these pathways. The effect of its inhibition by the FDA approved drug, lithium on AKI is still under study.Material & Methods: The current study was conducted on28 Male Sprague–Dawley rats. We classified the rats into groups. We induced acute kidney injury to rats with cisplatin. We administered lithium chloride to treat AKI in comparison with saline treatment. We have done renal functions and histopathological examinations to all rats enrolled in our study.Results: Single intraperitoneal injection of cisplatin (5 mg/kg) in rat induced acute kidney injury. The effect of lithium chloride treatment with dose (80 mg/kg) on serum creatinine and blood urea levels showed significant regression in the rising of serum creatinine and blood urea in lithium chloride treated rats in comparison to saline-treated rats. Pathological pictures and scores demonstrated an improvement in lithium chloride treated rats than saline-treated but results were not significant.Conclusion:Administration of lithium may be a promising treatment for acute kidney injury.Journal of Nobel Medical CollegeVolume 6, Number 2, Issue 11 (July-December, 2017) Page:14-19

Objective Our study aimed to investigate the possible protective effects of quercetin (QCT) on doxorubicin (DOX)-induced cardiotoxicity in rats. Background DOX is an antineoplastic drug that produces cardiotoxicity; it generates highly cytotoxic-free radicals that damage the cardiomyocytes. QCT is a plant flavonoid. QCT pretreatment reduces DOX-induced oxidative stress. Materials and methods Fifty-five adult rats were divided into four groups: group 1 (control) received saline (5 ml/kg) orally for 4 weeks; group 2 (DOX) received six doses of DOX intraperitoneally (2.5 mg/kg) on alternative days in the last 2 weeks; group 3 (QCT + DOX) received QCT orally (10 mg/kg once daily) for 4 weeks and DOX intraperitoneally (2.5 mg/kg) in the last 2 weeks as group 2, and group 4 (QCT) received QCT (10 mg/kg once daily) orally for 4 weeks. We measured the body weight, heart weight, and ECG parameters. Serum cardiac troponin-I (cTn-I), serum malondialdehyde (MDA), and total serum antioxidant capacity (TAC) have been estimated. In addition, histopathological changes of the rat heart were assessed. Results The DOX group showed significant ECG changes, significant increase in serum cTn-I (P Conclusion QCT may be a promising cardioprotective agent against DOX-induced cardiotoxicity due to its inhibition of cardiac apoptosis and oxidative stress.

Background Chronic renal failure (CRF) is a major public health problem worldwide. The pathophysiological basis of the disease and its complication include inflammation and oxidative stress, which are similar in humans and animals. In this study, we seek to develop new therapeutic modalities for CRF. Objective This study aimed to investigate the nephroprotective effects of curcumin (CUR) and/or sildenafil in adenine (AD) model of CRF. Materials and methods Rats were divided into five groups as follows: control naive group, AD group received AD 200 mg/kg/day orally to induce CRF, CUR group received CUR 200 mg/kg/day in addition to AD, sildenafil group received sildenafil 0.5 mg/kg/day in addition to AD, and combination group received combination of CUR 200 mg/kg/day and sildenafil 0.5 mg/kg/day in addition to AD. After consecutive 28 days of treatment, body weight, kidney index, and Doppler on renal artery assessments were done for all groups. In addition, kidney function tests and markers of oxidative stress were evaluated. Histopathological assessment of renal tissues and immunohistochemical staining for tumor necrosis factor-α were performed. Results CUR, sildenafil, and their combination significantly decreased body weight loss and urine volume and improved renal hemodynamic changes caused by AD. In addition, they significantly improved kidney function tests and biomarkers of oxidative stress. A significant down-regulation of tumor necrosis factor-α immunohistochemical expression was noted. They also brought histopathological changes induced by AD toward normal. Conclusion CUR and sildenafil may play a role in renal protection in AD-induced nephrotoxicity. The combined treatment showed better nephroprotective effect than either treatment alone did.

The aim of this study was to investigate the protective effect of montelukast (MTK) against prednisolone-induced hepatic injury in rats. Twenty-eight male albino rats were categorized into four equal groups. Group I served as the control group; group II: rats orally received prednisolone (5 mg·kg-1 ·d-1 ) for 30 days; groups III and IV: rats orally received MTK at 10 and 20 mg·kg-1 ·d-1 , respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes, hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic markers were evaluated, and the results were confirmed by histopathological examination. MTK showed significant hepatic protection evidenced by alleviated histological lesion and improvement of mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic changes induced by prednisolone, with more profound protection in higher MTK dose (20 mg·kg-1 ). In view of these findings, we can conclude that MTK may have hepatoprotective potential, beyond its therapeutic value for asthmatic patients during their course of corticosteroid therapy.

Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. I investigated the antidepressant effect of simvastatin (SMV) on diabetic rats. Rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were orally administered 0, 5, or 10 mg/kg of SMV daily for 14 days, then exposed to the forced swimming test (FST). Our results showed that diabetic rats had higher immobility duration than the CTR rats, and SMV decreased this depressive-like behavior in the diabetic rats. However, clomipramine lowered the immobility time in the CTR and STZ rats. STZ decreased serotonin concentration in the hippocampus, which was reversed by SMV and clomipramine. The dopamine concentration in the hippocampus decreased in the STZ groups compared with the CTR groups. However, SMV and clomipramine had no significant effect on the dopamine levels in either the CTR or STZ groups. Corticosterone levels were increased in the untreated STZ group; SMV and clomipramine significantly decreased corticosterone levels in the STZ groups, but had no effect on the CTR groups. In conclusion, SMV exerts an antidepressant-like effect on diabetic rats that are submitted to the FST. The antidepressant-like effect of SMV in the FST appears to be mediated, at least in part, by the biochemical changes to the blood levels of corticosterone and of serotonin concentration in the hippocampus.