Transforming iodoquinol into broad spectrum anti-tumor leads: Repurposing to modulate redox homeostasis.

We managed to repurpose the old drug iodoquinol to a series of novel anticancer 7-iodo-quinoline-5,8-diones. Twelve compounds were identified as inhibitors of moderate to high potency on an inhouse MCF-7 cell line, of which 2 compounds (5 and 6) were capable of reducing NAD level in MCF-7 cells in concentrations equivalent to half of their ICs, potentially due to NAD(P)H quinone oxidoreductase (NQO1) inhibition. The same 2 compounds (5 and 6) were capable of reducing p53 expression and increasing reactive oxygen species levels, which further supports the NQO-1 inhibitory activity.

Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2-dimethylhydrazine in rats.

Several studies have revealed that the combination of indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), and vitamin D reduces the risk of common types of cancers. Nonetheless, research on the deal concentrations used to test the impact of vitamin D on colon cancer is deficient. Along these lines, the aim of the present study was to evaluate the possible role of indomethacin and vitamin D as a preventative as well as a therapeutic operator for colon cancer growth induced by dimethylhydrazine (DMH) in male Albino rats.

Alcohol suppresses cardiovascular diurnal variations in male normotensive rats: Role of reduced PER2 expression and CYP2E1 hyperactivity in the heart.

Background And Aims: The molecular mechanism of the adverse effects of ethanol on diurnal cardiovascular regulation remains unknown. In separate studies, the cardiac circadian rhythm protein period-2 (PER2) confers cardioprotection and, in other organs, PER2 interaction with the ethanol-metabolizing enzyme CYP2E1 underlies, via heme oxygenase-1 (HO-1) upregulation, tissue injury/dysfunction. Here, we hypothesized that suppressed PER2 expression and elevated CYP2E1/HO-1 levels in the heart underlie the disrupted diurnal cardiovascular rhythm/function in alcohol-fed normotensive rats.

The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-κB axis.

One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-κB, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity.

Salvianolic Acid B Slows the Progression of Breast Cancer Cell Growth via Enhancement of Apoptosis and Reduction of Oxidative Stress, Inflammation, and Angiogenesis.

Breast cancer is the current leading cause of cancer death in females worldwide. Although current chemotherapeutic drugs effectively reduce the progression of breast cancer, most of these drugs have many unwanted side effects. Salvianolic acid B (Sal-B) is a bioactive compound isolated from the root of Danshen Radix with potent antioxidant and anti-inflammatory properties.

A dual role of 12/15-lipoxygenase in LPS-induced acute renal inflammation and injury.

Recent studies suggest a potential role of bioactive lipids in acute kidney injury induced by lipopolysaccharide (LPS). The current study was designed to determine the profiling activities of various polyunsaturated fatty acid (PUFA) metabolizing enzymes, including lipoxygenases (LO), cyclooxygenase, and cytochrome P450 in the plasma of LPS-injected mice using LC-MS. Heat map analysis revealed that out of 126 bioactive lipids screened, only the 12/15-LO metabolite, 12-HETE, had a significant (2.

Synergistic antiproliferative effects of curcumin and celecoxib in hepatocellular carcinoma HepG2 cells.

Hepatocellular carcinoma (HCC) is still a leading cancer killer in the community. Molecular targeted therapy with celecoxib (CXB) has shown promising antitumor effects; however, its use may be limited due to serious side effects. Curcumin (CUR) has also shown beneficial effects against HCC.

Influence of the selective COX-2 inhibitor celecoxib on sex differences in blood pressure and albuminuria in spontaneously hypertensive rats.

We previously reported that female spontaneously hypertensive rats (SHR) have greater cyclooxygenase-2 (COX-2) expression in the renal medulla and enhanced urinary excretion of prostaglandin (PG) E (PGE) metabolites compared to male SHR. Based on the role of COX-2-derived prostanoids in the regulation of cardiovascular health, the aim of the current study was to test the hypothesis that blood pressure (BP) in female SHR is more sensitive to COX-2 inhibition than in males. Seven week old male and female SHR were implanted with telemetry transmitters for continuous BP recording.

Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-κB mediated inflammation and apoptosis in experimental gastric ulcer.

Non-steroidal anti-inflammatory drugs (NSAIDs) consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Silymarin (SM) is a flavonoid mixture with anti-oxidant and anti-inflammatory activities which explain its protective role against hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated.

Ameliorative effect of gossypin against gentamicin-induced nephrotoxicity in rats.

Aim: Gentamicin (GEN) is an aminoglycoside antibiotic employed in treatment of life-threatening gram-negative infections, but one of its major side effects is the induction of nephrotoxicity. Therefore, the aim of this work was to scrutinize the possible protective effect of gossypin against GEN-induced nephrotoxicity.

Method: Rats were randomly divided into four groups.

Transforming Growth Factor-β1/Smad3 Signaling and Redox Status in Experimentally Induced Nephrotoxicity: Impact of Carnosine.

Unlabelled: Exposure to various organic compounds including drugs and environmental toxins causes cellular damage through generation of free radicals. Carnosine a dipeptide was used in this study to evaluate its effect against CCl4-induced nephrotoxicity. Sixty male albino rats were involved in this study and were equally divided into four groups.

N-acetylcysteine a possible protector against indomethacin-induced peptic ulcer: crosstalk between antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

This study investigated the gastroprotective effects of N-acetylcysteine (NAC) against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg). 50 male albino rats were allocated into 5 equal groups: control group received normal saline orally, indomethacin group rats received normal saline orally for 5 days and indomethacin (50 mg/kg) on the last day, ranitidine group received ranitidine (reference drug) orally for 5 days (50 mg/kg) before receiving indomethacin (50 mg/kg) on the last day, and NAC groups received NAC orally at 300 and 500 mg/kg, respectively, for 5 days before receiving indomethacin (50 mg/kg) on the last day.

Meloxicam fails to augment the reno-protective effects of soluble epoxide hydrolase inhibition in streptozotocin-induced diabetic rats via increased 20-HETE levels.

The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.

Novel molecular triggers underlie valproate-induced liver injury and its alleviation by the omega-3 fatty acid DHA: role of inflammation and apoptosis.

Background/aim: Hepatic injury is a hallmark adverse reaction to Valproate (VPA), a common used drug in the management of numerous CNS disorders, including epilepsy. DHA has a myriad of health benefits, including renal- and hepato-protective effects. Unfortunately, however, the underpinnings of such liver-pertinent VPA- and DHA-actions remain largely undefined.

Irbesartan, an angiotensin II receptor antagonist, with selective PPAR-gamma-modulating activity improves function and structure of chemotherapy-damaged ovaries in rats.

Cyclophosphamide (CYP) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP induces granulosa cell apoptosis and oxidative stress. Irbesartan (IRB) is a unique ARB with a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonistic activity.