Zeba Farooqui

Protective effect of dietary flaxseed oil on arsenic-induced nephrotoxicity and oxidative damage in rat kidney.

Arsenic, a naturally occurring metalloid, is capable of causing acute renal failure as well as chronic renal insufficiency. Arsenic is known to exert its toxicity through oxidative stress by generating reactive oxygen species (ROS). Flaxseed, richest plant based dietary source of ω-3 polyunsaturated fatty acids (PUFAs) and lignans have shown numerous health benefits. Present study investigates the protective effect of flaxseed oil (FXO) on sodium arsenate (NaAs) induced renal damage. Rats prefed with experimental diets (Normal/FXO diet) for 14days, were administered NaAs (20mg/kg body weight i.p.) once daily for 4days while still on the experimental diets. NaAs nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. Administration of NaAs led to a significant decline in the specific activities of brush border membrane (BBM) enzymes both in kidney tissue homogenates and in the isolated membrane vesicles. Lipid peroxidation and total sulfhydryl groups were altered upon NaAs treatment, indicating the generation of oxidative stress. NaAs also decreased the activities of metabolic enzymes and antioxidant defence system. Histopathological studies supported the biochemical findings showing extensive damage to the kidney by NaAs. In contrast, dietary supplementation of FXO prior to and alongwith NaAs treatment significantly attenuated the NaAs-induced changes.

Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney

BACKGROUND Nephrotoxicity is a severe complication in patients undergoing cisplatin (CP) chemotherapy. Previous studies in our lab have shown that administration of a single dose of CP results in decrease in the activities of brush border membrane (BBM) and free radical scavenging enzymes and induces oxidative stress in rat kidney. Nigella sativa, is one of the most revered medicinal plant known for its numerous health benefits. Nigella sativa seed/oil has been shown to improve kidney functions in animal models of acute kidney injury. OBJECTIVE The present study was undertaken to investigate whether Nigella sativa oil (NSO) can prevent the CP-induced nephrotoxic effects. RESULTS The effect of NSO was determined on CP induced alterations in various serum parameters and on enzymes of carbohydrate metabolism, BBM and antioxidant defense system in renal cortex and medulla. Administration of NSO (2ml/kg bwt. orally), prior to and following a single dose CP treatment (6mg/kg bwt. i.p), significantly attenuated the CP induced increase in serum creatinine (Scr) and blood urea nitrogen (BUN) and decrease in the activities of BBM enzymes in renal cortical and medullary homogenates as well as in isolated BBM vesicles (BBMV). NSO administration also precluded CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters. Histopathological observations showed extensive kidney damage in CP treated animals and remarkably reduced renal injury in CP and NSO co-treated group. CONCLUSION The biochemical and histological data suggest a protective effect of NSO against CP-induced acute kidney injury.

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on brush border membrane enzymes, carbohydrate metabolism and antioxidant system in rat intestine

Cisplatin (CP) is an effective chemotherapeutic agent that induces gastrointestinal toxicity. Nigella sativa oil (NSO) has been shown to be beneficial in a wide range of gastrointestinal disorders. The present study investigates the possible protective effect of NSO on CP-induced gastrointestinal toxicity. NSO administration (2ml/kg bwt, orally), prior to and following, a single dose CP treatment (6mg/kg bwt. ip), significantly attenuated the CP-induced decrease in brush border membrane (BBM) enzyme activities in intestinal homogenates and BBM vesicles (BBMV). NSO administration also mitigated CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters in the intestine. The results suggest that NSO by empowering the endogenous antioxidant system improves intestinal redox and metabolic status and restores BBM integrity in CP treated rats. Histopathological studies supported the biochemical findings. Thus, NSO may help prevent the accompanying gastrointestinal dysfunction in CP chemotherapy.

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

Highlights • NSO improves the endogenous antioxidant status and metabolic activity of liver.• NSO protects the liver against CP generated free radical attack.• Oral administration of NSO ameliorates the hepatotoxicity induced by CP treatment.

Oral administration of thymoquinone mitigates the effect of cisplatin on brush border membrane enzymes, energy metabolism and antioxidant system in rat intestine

Cisplatin (CP) is a widely used chemotherapeutic agent that elicits severe gastrointestinal toxicity. Nigella sativa, a member of family Ranunculaceae, is one of the most revered medicinal plant known for its numerous health benefits. Thymoquinone (TQ), a major bioactive component derived from the volatile oil of Nigella sativa seeds, has been shown to improve gastrointestinal functions in animal models of acute gastric/intestinal injury. In view of this, the aim of the present study was to investigate the protective effect of TQ on CP induced toxicity in rat intestine and to elucidate the mechanism underlying these effects. Rats were divided into four groups viz. control, CP, TQ and CP+TQ. Animals in CP+TQ and TQ groups were orally administered TQ (1.5mg/kg bwt) with and without a single intraperitoneal dose of CP (6mg/kg bwt) respectively. The effect of TQ was determined on CP induced alterations in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in rat intestine. TQ administration significantly mitigated CP induced decline in the specific activities of BBM marker enzymes, both in the mucosal homogenates and in the BBM vesicles (BBMV) prepared from intestinal mucosa. Furthermore, TQ administration restored the redox and metabolic status of intestinal mucosal tissue in CP treated rats. The biochemical results were supported by histopathological findings that showed extensive damage to intestine in CP treated rats and markedly preserved intestinal histoarchitecture in CP and TQ co-treated group. The biochemical and histological data suggest a protective effect of TQ against CP-induced gastrointestinal damage. Thus, TQ may have a potential for clinical application to counteract the accompanying gastrointestinal toxicity in CP chemotherapy.

Cisplatin-induced gastrointestinal toxicity: An update on possible mechanisms and on available gastroprotective strategies

Abstract Cisplatin (cis‐diamminedichloroplatinum [II], CP) is most widely prescribed in chemotherapy and efficaciously treats diverse human cancers, with remission rates > 90% in testicular cancers. However, clinical use of CP is associated with numerous untoward side effects, in particular, at the gastrointestinal level that reduces the therapeutic efficacy of CP and often results in withdrawal of its clinical usage in long term cancer chemotherapy. Substantial strides have been made to identify effective protective strategies against CP‐induced nephrotoxicity, hepatotoxicity and ototoxicity. Unfortunately, very limited studies have focused on CP‐induced gastrointestinal toxicity and advances in developing potent gastroprotective strategies/agents are still lacking. The current article reviews the metabolism and pharmacokinetics of CP, mechanisms underlying CP‐induced gastrointestinal toxicity and lastly displays the potential approaches including plant‐derived agents (phytochemicals) utilized to counteract CP‐induced gastrointestinal dysfunction. Furthermore, the gastroprotective agents described in the experimental literature have shown partial protection against CP‐induced intestinal damage. This stresses the need to ascertain new information on the underlying mechanism and to discover novel combinatorial strategies for the abrogation of CP‐induced gastrointestinal toxicity.

Effect of Fasting on Enzymes of Carbohydrate Metabolism, Brush Border Membrane and on Transport Functions in Superficial and Juxta-Medullary Cortex of Rat Kidney

The effect of 1, 3 and 5-day fasting was studied on serum parameters; enzymes of brush border membrane and carbohydrate metabolism; transport of Pi and proline in different parts of the rat kidney. Fasting decreased the activities of lactate dehydrogenase, malate dehydrogenase but increased the activities of glucose-6-phosphatase and fructose 1,6-bisphosphatase; glucose-6-phosphate dehydrogenase and malic enzyme. These observations suggest that the degradation of glucose is decreased but its production by gluconeogenesis is enhanced upon fasting. Fasting led to significant decrease in the specific activities of Brush Border Membrane (BBM) enzymes, alkaline phosphatase and γ-glutamyl transferase in BBM vesicles prepared from superficial and juxta-medullary cortex. The transport of Pi was also decreased albeit differentially in these BBM preparations. Kinetic studies revealed that the activity of BBM enzymes and Pi transport decreased due to changes in Vmax and Km values. The results show that fasting caused significant decrease in metabolic enzymes involved in energy generation that led to decreased transport functions of the kidney.

Effect of fasting and fasting-refeeding on the structure, metabolism and transport functions of renal cortical proximal tubules from different kidney regions

The effect of fasting and fasting-re-feeding was studied on certain serum parameters; enzymes of brush border membrane and carbohydrate metabolism; transport of Pi in different anatomical parts of rat kidney. Fasting decreased the activities of lactate dehydrogenase (LDH), malate dehydrogenase (MDH) but increased the activities of glucose-6-phosphatase (G6Pase) and fructose 1, 6-bisphosphatase (FBPase); glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME). Activities of brush border membrane (BBM) and the transport of Pi in BBM vesicles prepared from superficial and juxta-medullary cortex were also decreased. The feeding of a normal diet to fasted rats reversed the effect of fasting on various parameters. The activities of BBM enzymes and Pi transport elevated to above fasting levels close to control values. Kinetic parameters determined for BBM enzymes and Pi transport affected by fasting and/or re-feeding by alteration in the Vmax and Km values. The enzymes of glucose degradation decreased but those of its production increased by fasting were also returned back towards control values by re-feeding. Serum Pi, phospholipids and cholesterol affected by fasting were also normalized by re-feeding. The results show that fasting caused significant decrease in metabolic enzymes involved in energy generation caused decrease in transport functions of the kidney but re-feeding could ameliorate the effect of fasting. In conclusion, the results show that the kidney can adapt too much greater extent under acute situations Abbreviations: AlkPase: Alkaline phosphatase; BBM: Brush border membrane; BUN: Blood urea nitrogen; BBMV: Brush border membrane vesicle; FBPase: Fructose 1,6-bisphosphatase; G6PDH: Glucose-6-phosphate dehydrogenase; GGTase: ɤ-glutamyl transferase; HK: Hexokinase; HMP: Hexose monophosphate; JMC: Juxtamedullary cortex; LDH: Lactate dehydrogenase; MDH: Malate dehydrogenase; ME: Malic enzyme; NADPH: Nicotinamide adenine dinucleotide phosphate reduced; NADP: Nicotinamide adenine dinucleotide phosphate; SC: Superficial cortex; WC: Whole cortex