Reversal of fluoride induced cell injury through elimination of fluoride and consumption of diet rich in essential nutrients and antioxidants

The objective of the present communication is to address the issues concerning reversal of fluoride induced cell injury and disease (i.e. fluorosis) through the elimination of fluoride and consumption of a diet containing essential nutrients and antioxidants. Humans afflicted with fluorosis, as a result of consuming fluoride contaminated water or food, have been investigated. Hospital based diagnostic procedure for early detection of fluorosis, through retrieval of history, clinical complaints, testing of blood, urine and drinking water for fluoride using ion selective electrode technology, along with X-ray of the forearm have been carried out. Confirmed cases of fluorosis were introduced to an intervention protocol consisting of (1) provision of safe drinking water with fluoride levels less than 1 mg/L and (2) counselling on nutritional supplementation with focus on adequate intake of calcium, vitamins C, E and antioxidants. The patients were monitored at frequent intervals up to one year and the results are reported. With a standardized early diagnosis, elimination of fluoride intake and supplementation of a diet rich in essential nutrients and antioxidants, we have shown that the fluorosis can be reversed.     

Influence of the antioxidants vitamin E and idebenone on retinal cell injury mediated by chemical ischemia, hypoglycemia, or oxidative stress

A role for the antioxidants vitamin E and idebenone in decreasing retinal cell injury, after metabolic inhibition induced by chemical ischemia and hypoglycemia, was investigated and compared with oxidative stress conditions. Preincubation of the antioxidants, vitamin E (20 microM) and idebenone (10 microM), effectively protected from retinal cell injury after oxidative stress or hypoglycemia, whereas the protection afforded after postincubation of both antioxidants was decreased. Delayed retinal cell damage, mediated by chemical ischemia, was attenuated at 10 or 12 h postischemia, only after exposure to the antioxidants during all the experimental procedure. An antagonist of the N-methyl-D-aspartate (NMDA) receptors, an inhibitor of nitric oxide synthase (NOS) or a blocker of L-type Ca2+ channels were ineffective in reducing cell injury induced by chemical ischemia, hypoglycemia or oxidative stress. Oxidative stress and hypoglycemia increased (about 1.2-fold) significantly the fluorescence of the probe DCFH2-DA, that is indicative of intracellular ROS formation. Free radical generation detected with the probe dihydrorhodamine 123 (DHR 123) was enhanced after oxidative stress, chemical ischemia or hypoglycemia (about 2-fold). Nevertheless, the antioxidants vitamin E or idebenone were ineffective against intracellular ROS generation. Cellular energy charge decreased greatly after chemical ischemia, was moderately affected after hypoglycemia, but no significant changes were observed after oxidative stress. Preincubation with vitamin E prevented the changes in energy charge upon 6 h posthypoglycemia. We can conclude that irreversible changes occurring during chemical ischemia mainly reflect the alterations taking place at the ischemic core, whereas hypoglycemia situations may reflect changes occurring at the penumbra area, whereby vitamin E or idebenone may help to increase cell survival, exerting a beneficial neuroprotective effect.     

Dynamics analyses of nutrients consumption and flavonoids accumulation in cell suspension culture of Glycyrrhiza inflata

The dynamics of biomass accumulation, production of flavonoids and consumption of carbon, nitrogen and phosphate were investigated in Glycyrrhiza inflata Batal cell suspensions cultivated in flasks. Biomass accumulation exhibited a “S”-shape curve in each culture cycle, with the greatest values obtained on day 21 (16.4 and 232.4 g dm⁻³ of dry and fresh mass, respectively). Similarly, flavonoids production also got to a peak of 95.7 mg dm⁻³ on day 21. Sucrose was decomposed to reducing sugars which were almost used up on day 22. Nitrate and phosphate in the medium were almost exhausted on day 18 and 10, respectively, while ammonium still maintained at concentration 100 mg dm⁻³ when the cells were harvested. Consequently, the proportion of ammonium to nitrate in the medium should be optimized for higher flavonoid production.     

Adaptive contraction of diet breadth affects sexual maturation and specific nutrient consumption in an extreme generalist omnivore

Animals balance their intake of specific nutrients, but little is known about how they do so when foraging in an environment with toxic resources and whether toxic foods promote adaptations that affect life history traits. In German cockroach (Blattella germanica) populations, glucose aversion has evolved in response to glucose‐containing insecticidal baits. We restricted newly eclosed glucose‐averse (GA) and wild‐type (WT) female cockroaches to nutritionally defined diets varying in protein‐to‐carbohydrate (P : C) ratio (3 : 1, 1 : 1, or 1 : 3) or gave them free choice of the 3 : 1 and 1 : 3 diets, with either glucose or fructose as the sole carbohydrate source. We measured consumption of each diet over 6 days and then dissected the females to measure the length of basal oocytes in their ovaries. Our results showed significantly lower consumption by GA compared to WT cockroaches when restricted to glucose‐containing diets, but also lower fructose intake by GA compared to WT cockroaches when restricted to high fructose diets or given choice of fructose‐containing diets. Protein intake was regulated tightly regardless of carbohydrate intake, except by GA cockroaches restricted to glucose‐containing diets. Oocyte growth was completely suppressed in GA females restricted to glucose‐containing diets, but also significantly slower in GA than in WT females restricted to fructose‐containing diets. Our findings suggest that GA cockroaches have adapted to reduced diet breadth through endocrine adjustments which reduce requirements for energetic fuels. Our study illustrates how an evolutionary change in the chemosensory system may affect the evolution of other traits that govern animal life histories.     

Aluminium Fluoride induced changes in chlorophyll a fluorescence,antioxidants and psb A gene expression of Brassica juncea cultivars

In present study, the effects of combined Aluminium and Fluoride (AlF) stress on chlorophyll a fluorescence, photosynthetic pigments, antioxidant system and psb A gene expression are first time reported in four Brassica juncea cultivars (CS-14, Pusa-Tarak, Bio-902 and Laxmi). Each cultivar was exposed to soil supplemented with AlF (0, 50?+?25, 100?+?50 and 150?+?75?mgkg^?1). Lowest decline in the chlorophyll content, saturating photosynthetically active photon flux density, maximum apparent electron transport rate and effective quantum yield (PSII) under AlF was observed in Pusa-Tarak followed by CS-14, Bio-902 and Laxmi. The improved performance of the cultivar Pusa-Tarak under AlF stress was accompanied by an increase in proline level and enzymes activity of catalase and ascorbate peroxidase. However, significant increase in superoxide dismutase activity was observed in cultivar Laxmi. We also observed that AlF inhibits psb A gene expression to a lesser extent in tolerant cultivar Pusa-Tarak in comparison to susceptible cultivar Laxmi.     

Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP + AG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub‐epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP‐induced oxidative stress, decrease in the activities of anti‐oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP‐induced bladder damage. Copyright © 2008 John Wiley & Sons, Ltd.     

Salicylic acid mitigates salt induced toxicity through the modifications of biochemical attributes and some key antioxidants in capsicum annuum

Abiotic stress causes extensive loss to agricultural yield production worldwide. Salt stress is one of them crucial factor which leads to decreased the agricultural production through detrimental effect on growth and development of crops. In our study, we examined the effect of a defense growth substance, salicylic acid (SA 1 mM) on mature vegetative (60 Days after sowing) and flowering (80 DAS) stage of Pusa Sadabahar (PS) variety of Capsicum annuum L. plants gown under different concentrations of NaCl (25, 50, 75, 100 and 150 mM) and maintained in identical sets in pots during the whole experiment. Physiological studies indicated that increase in root & shoot length, fresh & dry weight, number of branches per plant, and yield (number of fruits per plant) under salt + SA treatment. Biochemical studies, enzymatic antioxidants like CAT, POX, and non-enzymatic antioxidant such as ascorbic acid (AsA content), carotenoids, phenolics, besides other defense compounds like proline, protein, chlorophyll contents were studied at 10 days after treatment at the mature vegetative and flowering stage. The addition of SA led to lowering of in general, all studied parameters in the mature vegetative stage but increased the same during the flowering stage, especially in the presence of NaCl; although the control I (without SA and NaCl) remained lower in value than control II (with SA, without NaCl). Interestingly, total phenolics were higher in control I (without SA or NaCl) whereas chlorophylls were higher in treatments with SA and NaCl. Thus, physiological concentration of SA (1 mM) appears to be significantly effective against salt stress during the flowering stage. In addition, during the mature vegetative stage, however, proline accumulates in SA treated sets, to help in developing NaCl-induced drought stress tolerance.     

Specific inhibition of hypoxia inducible factor 1 exaggerates cell injury induced by in vitro ischemia through deteriorating cellular redox environment

Hypoxia inducible factor 1 (HIF-1) has been suggested to play a critical role in the fate of cells exposed to hypoxic stress. However, the mechanism of HIF-1-regulated cell survival is still not fully understood in ischemic conditions. Redox status is critical for decisions of cell survival, death and differentiation. We investigated the effects of inhibiting HIF-1 on cellular redox status in SH-SY5Y cells exposed to hypoxia or oxygen and glucose deprivation (OGD), coupled with cell death analyses. Our results demonstrated that inhibiting HIF-1α expression by HIF-1α specific small interfering RNA (siRNA) transfection increased reactive oxygen species generation, and transformed the cells to more oxidizing environments (low GSH/GSSG ratio, low NADPH level) under either hypoxic or OGD exposure. Cell death increased dramatically in the siRNA transfected cells, compared to non-transfected cells after hypoxic/OGD exposures. In contrast, increasing HIF-1α expression by desferrioxamine, a metal chelator and hydroxylase inhibitor, induced a more reducing environment (high GSH/GSSG ratio, high NADPH level) and reduced cell death. Further studies showed that HIF-1 regulated not only glucose transporter-1 expression, but also the key enzymes of the pentose phosphate pathway such as glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. These enzymes are important in maintaining cellular redox homeostasis by generating NADPH, the primary reducing agent in cells. Moreover, catalase significantly decreased cell death in the siRNA-transfected cells induced by hypoxia and OGD. These results suggest that maintenance of cellular redox status by HIF-1 protects cells from hypoxia and ischemia mediated injuries.     

Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet

Endothelial dysfunction develops as a result of oxidative stress and is responsible for diabetic vascular complications. We investigated the effects of selenium on endothelial dysfunction and oxidative stress in type 2 diabetic rats. Male Wistar rats were divided into five groups: controls, untreated diabetics, and diabetics treated with 180, 300, 500 mcg/kg selenium each day. Diabetes was induced by a single intraperitoneal injection of low dose streptozotocin to rats fed a high fat diet. Endothelium-dependent and -independent relaxations were measured in the thoracic aorta. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and endothelial nitric oxide synthase (eNOS) mRNA expressions were analyzed using real-time polymerase chain reaction (RT-PCR). Fasting blood glucose, lipid profile, lipid oxidation, insulin and nitric oxide were measured in blood samples. Malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase levels were measured in liver samples. RT-PCR showed that selenium reversed increased NADPH oxidase expression and decreased eNOS expression to control levels. Selenium also improved the impairment of endothelium-dependent vasorelaxation in the diabetic aorta. Selenium treatment significantly decreased blood glucose, cholesterol and triglyceride levels, and enhanced the antioxidant status in diabetic rats. Our findings suggest that selenium restores a normal metabolic profile and ameliorates vascular responses and endothelial dysfunction in diabetes by regulating antioxidant enzyme and nitric oxide release.     

Differential effects of vitamin E and three hydrophilic antioxidants on the actinomycin D-induced and colcemid-accelerated apoptosis in human leukemia CMK-7 cell line

The actinomycin D (AD)-induced apoptosis in human leukemia CMK-7 cell line is greatly accelerated by microtubule disruption with colcemid (CL). We studied the effect of antioxidants on this apoptosis in order to learn how the universal signal mediators, reactive oxygen species (ROS), are involved. Caspase-3 activation and DNA fragmentation were both suppressed by vitamin E (VE), t-butylhydroxyanisole, and luteolin. The ROS formation in the AD treatment was evidenced by flow cytometry, and further supported by suppression of caspase-3 activation by superoxide radical-forming enzyme inhibitors (TTFA, rotenone, and DPI). The inhibition of apoptosis by VE was completed during the initial 1-h treatment with AD, but it did not appear when VE was added with CL to washed cells after AD treatment. Luteolin, an iron chelator PDTC, and a water-soluble VE analogue, trolox, inhibited the apoptosis when added with CL after the AD treatment. Western blot analysis showed that the proteolytic cleavage of procaspase-9 and procaspase-3 were both inhibited when VE was added with AD or when luteolin was added with CL, and that the cytochrome c liberation was suppressed by both antioxidants. This result implies that the ROS are initially formed in lipophilic environments (e.g. mitochondrial membrane) and then they diffuse into an aqueous environment (i.e. cytoplasm) where they promote the apoptotic process in combination with the cytoskeletal disruption. Thus, the different antioxidants are effective to scavenge ROS for preventing the apoptosis in its different phases.     

PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration

This study was designed to identify the molecular mechanisms of phosphatidylinositol 3-kinase (PI3K)-induced actin filament remodeling and cell migration. Expression of active forms of PI3K, v-P3k or Myr-P3k, was sufficient to induce actin filament remodeling to lead to an increase in cell migration, as well as the activation of Akt in chicken embryo fibroblast (CEF) cells. Either the inhibition of PI3K activity using a PI3K-specific inhibitor, LY-294002, or the disruption of Akt activity restored the integrity of actin filaments in CEF cells and inhibited PI3K-induced cell migration. We also found that expression of an activated form of Akt (Myr-Akt) was sufficient to remodel actin filaments to lead to an increase in cell migration, which was unable to be inhibited by the presence of LY-294002. Furthermore, we found that p70S6K1 kinase was a downstream molecule that can mediate the effects of both PI3K and Akt on actin filaments and cell migration. Overexpression of an active form of p70S6K1 was sufficient to induce actin filament remodeling and cell migration in CEF cells, which requires Rac activity. These results demonstrate that activation of PI3K activity alone is sufficient to remodel actin filaments to increase cell migration through the activation of Akt and p70S6K1 in CEF cells. phosphatidylinositol 3-kinase; Rac; actin filaments     

Peroxiredoxin IV plays a critical role in cancer cell growth and radioresistance through the activation of the Akt/GSK3 signaling pathways

High levels of redox enzymes have been commonly observed in various types of human cancer, although whether and how the enzymes contribute to cancer malignancy and therapeutic resistance have yet to be understood. Peroxiredoxin IV (Prx4) is an antioxidant with bona fide peroxidase and molecular chaperone functions. Here, we report that Prx4 is highly expressed in prostate cancer patient specimens, as well as established prostate cancer cell lines, and that its levels can be further stimulated through the activation of androgen receptor signaling. We used lentivirus-mediated shRNA knockdown and CRISPR-Cas9 based KO techniques to establish Prx4-depleted prostate cancer cells, which showed delayed cell cycle progression, reduced rate of cell proliferation, migration, and invasion compared to control cells. In addition, we used proteome profiler phosphokinase arrays to identify signaling changes in Prx4-depleted cells; we found that loss of Prx4 results in insufficient phosphorylation of both Akt and its downstream kinase GSK3α/β. Moreover, we demonstrate that Prx4-depleted cells are more sensitive to ionizing radiation as they display compromised ability to scavenge reactive oxygen species and increased accumulation of DNA damage. In mouse xenograft models, we show depletion of Prx4 leads to significant suppression of tumor growth, and tumors formed by Prx4-depleted cells respond more effectively to radiation therapy. Our findings suggest that increased levels of Prx4 contribute to the malignancy and radioresistance of prostate cancer through the activation of Akt/GSK3 signaling pathways. Therefore, strategies targeting Prx4 may be utilized to potentially inhibit tumor growth and overcome radioresistance in prostate cancer.     

Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages

The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 μg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities.     

Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits

A high-performance liquid chromatography (HPLC) method to determine malondialdehyde (MDA) as the 2,4-dinitrophenylhydrazine (DNPH) derivative was applied to biological samples (serum and liver homogenates). Since MDA is considered a presumptive biomarker for lipid peroxidation in live organisms, a model for nutritionally induced oxidative stress (hypercholesterolemic rats) was studied in comparison with normocholesterolemic animals. The effect of diet supplementation with fruits rich in antioxidant polyphenols was assessed. The proposed method showed to be precise and reproducible, as well as sensitive enough to reflect differences in the oxidative status in vivo. A significant decrease of serum and liver MDA concentrations in animals fed diets containing 0.3% of polyphenols from strawberry, cocoa or plum was observed in the normocholesterolemic groups. This reduction was especially noteworthy in the hypercholesterolemic animals, with increased MDA levels indicating enhanced lipid peroxidation in the controls, yet with values parallel to the normocholesterolemic groups in animals fed the polyphenol-rich diets. These results point out the beneficial effects of phenolic antioxidants from fruits in preventing oxidative damage in vivo.     

Costs of an induced immune response on sexual display and longevity in field crickets

Immune system activation may benefit hosts by generating resistance to parasites. However, natural resources are usually limited, causing a trade-off between the investment in immunity and that in other life-history or sexually selected traits. Despite its importance for the evolution of host defense, state-dependent fitness costs of immunity received little attention under natural conditions. In a field experiment we manipulated the nutritional condition of male field crickets Gryllus campestris and subsequently investigated the effect of an induced immune response through inoculation of bacterial lipopolysaccharides. Immune system activation caused a condition-dependent reduction in body condition, which was proportional to the condition-gain during the preceding food-supplementation period. Independent of nutritional condition, the immune insult induced an enduring reduction in daily calling rate, whereas control-injected males fully regained their baseline level of sexual signaling following a temporary decline. Since daily calling rate affects female mate choice under natural conditions, this suggests a decline in male mating success as a cost of induced immunity. Food supplementation enhanced male life span, whereas the immune insult reduced longevity, independent of nutritional status. Thus, immune system activation ultimately curtails male fitness due to a combined decline in sexual display and life span. Our field study thus indicates a key role for fitness costs of induced immunity in the evolution of host defense. In particular, costs expressed in sexually selected traits might warrant the honest advertisement of male health status, thus representing an important mechanism in parasite-mediated sexual selection.     

Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury

Understanding the molecular pathway(s) of antioxidant gene regulation is of crucial importance for developing antioxidant-inducing agents for the intervention of oxidative cardiac disorders. Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 enzymes in cardiac fibroblasts. The basal expression of a scope of key cellular antioxidants and phase 2 enzymes was significantly lower in cardiac fibroblasts derived from Nrf2-/- mice than those from wild type control. These include catalase, reduced glutathione (GSH), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). Incubation of Nrf2+/+ cardiac fibroblasts with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of superoxide dismutase (SOD), catalase, GSH, GR, glutathione peroxidase (GPx), GST, and NQO1. The inducibility of SOD, catalase, GSH, GR, GST, and NQO1, but not GPx by D3T was completely abolished in Nrf2-/- cells. The Nrf2-/- cardiac fibroblasts were much more sensitive to reactive oxygen and nitrogen species-mediated cytotoxicity. Upregulation of antioxidants and phase 2 enzymes by D3T in Nrf2+/+ cardiac fibroblasts resulted in a dramatically increased resistance to the above species-induced cytotoxicity. In contrast, D3T-treatment of the Nrf2-/- cells only provided a slight cytoprotection. Taken together, this study demonstrates for the first time that Nrf2 is critically involved in the regulation of the basal expression and chemical induction of a number of antioxidants and phase 2 enzymes in cardiac fibroblasts, and is an important factor in controlling cardiac cellular susceptibility to reactive oxygen and nitrogen species-induced cytotoxicity.     

Temperature-dependent electrical resistivity of the hornet cuticle: Changes induced by colchicine and purine in the diet

Various cuticular areas of the Oriental hornet (Vespa orientalis) were measured for their electrical resistivity within the range of 3–40°C. It was found that: (1) the electrical resistivity is temperature dependent; (2) there are no significant differences in this respect between hornets collected in different regions; (3) there are no differences in the electrical resisitivity between the yellow and brown areas of the cuticle in control hornets; (4) there are however, significant changes in resistance between the yellow and brown strips of hornets fed on purine; (5) hornets fed on colchicine reach a minimum resistance at a higher temperature than do the control hornets; and (6) hornets fed on purine reach a minimum resistance at a lower temperature. It is suggested that the cuticular changes in resistivity at different temperatures reflect the hornets' mechanism of detecting and adjusting to changes in the ambient temperature.     

Deficiency of apoptosis‐stimulating protein two of p53 ameliorates acute kidney injury induced by ischemia reperfusion in mice through upregulation of autophagy

Acute kidney injury (AKI) has become a common disorder with a high risk of morbidity and mortality, which remains major medical problem without reliable and effective therapeutic intervention. Apoptosis‐stimulating protein two of p53 (ASPP2) is a proapoptotic member that belongs to p53 binding protein family, which plays a key role in regulating apoptosis and cell growth. However, the role of ASPP2 in AKI has not been reported. To explore the role of ASPP2 in the progression of AKI, we prepared an AKI mouse model induced by ischaemia reperfusion (I/R) in wild‐type (ASPP2^+/+) mice and ASPP2 haploinsufficient (ASPP2^+/?) mice. The expression profile of ASPP2 were examined in wild‐type mice. The renal injury, inflammation response, cellular apoptosis and autophagic pathway was assessed in ASPP2^+/+ and ASPP2^+/? mice. The renal injury, inflammation response and cellular apoptosis was analysed in ASPP2^+/+ and ASPP2^+/? mice treated with 3‐methyladenine or vehicle. The expression profile of ASPP2 showed an increase at the early stage while a decrease at the late stage during renal injury. Compared with ASPP2^+/+ mice, ASPP2 deficiency protected mice against renal injury induced by I/R, which mainly exhibited in slighter histologic changes, lower levels of blood urea nitrogen and serum creatinine, and less apoptosis as well as inflammatory response. Furthermore, ASPP2 deficiency enhanced autophagic activity reflecting in the light chain 3‐II conversion and p62 degradation, while the inhibition of autophagy reversed the protective effect of ASPP2 deficiency on AKI. These data suggest that downregulation of ASPP2 can ameliorate AKI induced by I/R through activating autophagy, which may provide a novel therapeutic strage for AKI.