Comparative study of melasma in patients before and after treatment based on lipomics.

BACKGROUND: Skin barrier alterations play a crucial function in melasma development. Past researches have demonstrated variations in lipid content between the epidermis of melasma lesions and normal tissues, along with the varied expression of lipid-related genes in melasma. This study aimed to analyze the lipidome profiles of skin surface lipids (SSL) in patients with melasma before and after treatment to understand associated abnormalities. METHODS: Melasma was treated with tranexamic acid orally and hydroquinone cream topically. Disease was assessed using the Melasma Area and Severity Index (MASI), and the impact to life was evaluated with Melasma Quality of Life (MELASQoL) score. Epidermal melanin particles were observed using reflection confocal microscopy (RCM), whereas epidermal pigment and blood vessel morphology were observed using dermoscopy, and SSL samples were collected. Specific information regarding alterations in lipid composition was obtained through multivariate analysis of the liquid chromatography-mass spectrometry data. RESULTS: After treatment, patients with melasma exhibited decreased MASI and MELASQoL scores (P < 0.001); RCM revealed reduced melanin content in the lesions, and dermoscopy revealed fewer blood vessels. Fifteen lipid subclasses and 382 lipid molecules were identified using lipidomic assays. The expression levels of total lipids, phosphatidylcholine, and phosphatidylethanolamine in the melasma lesions decreased after treatment (P < 0.05). CONCLUSION: This study revealed alterations in the SSL composition after effective melasma treatment, suggesting a compensatory role for lipids in melasma barrier function. The mechanism involving SSL and the lipid barrier, which influences melasma's occurrence, needs further elucidation.

Differential diagnosis and management of hyperpigmentation.

There is an increasing recognition of ethnic dermatology to reflect the increase in skin of colour (SOC) populations in the UK. Hyperpigmentary disorder is one of the commonest skin concerns in SOC but there has been limited training available in this field of dermatology. Variations in skin colour are genetically determined by the amount of melanin content, the eumelanin/pheomelanin ratio and the size of melanosomes, but is also influenced by other factors such as hormones and extrinsic factors such as ultraviolet radiation. Hyperpigmentation is a broad term to describe increased pigmentation in the skin, and making a correct diagnosis is an important first step in the successful management of hyperpigmentary disorders. A systematic approach based on the disease pathogenesis (e.g. reactive vs. nonreactive, increased melanin vs. increased number of cells or epidermal vs. dermal pigmentation) aided by a detailed history and clinical examination is the best way to diagnose a hyperpigmentary disorder. Based on its pathogenesis, management can be planned. For epidermal hyperpigmentation caused by increased melanin, topical skin-lightening agents targeting inhibition of tyrosinase or melanosome transfer and promotion of keratinocyte turnover can be used. Hydroquinone-containing cream is the gold-standard treatment for epidermal hyperpigmentation. Alternative treatments include laser toning or chemical peels. However, increased dermal pigmentation is more challenging to target with topical treatments. If hyperpigmentation is due to increased numbers of melanocytes or keratinocytes, high-fluence laser is the most appropriate treatment method.

The effect of Nrf2 activators tBHQ and 4-octyl itaconate on the nucleus pulposus cell degeneration.

OBJECTIVE: The present study aimed to investigate the impact of two Nrf2 agonists, tBHQ and 4-Octyl Itaconate, on nucleus pulposus (NP) degeneration and explore the underlying mechanism. PATIENTS AND METHODS: We isolated the NP cells from the disc tissue of disc herniation patients. NP cells were pretreated with an adequate dose of tBHQ, Itaconate, or the mixture of them, and then subjected to the Lipopolysaccharides (LPS) stimulation to induce degeneration. Besides, the Nrf2 gene silenced NP cells were also used as a comparison. Moreover, the LPS-treated NP cells were also cultured in the mix of tBHQ and Itaconate to determine whether the agonists affected reverse degeneration. RESULTS: LPS treatment suppressed Nrf2 expression and induced the NP cell degeneration with a decrease of cell viability and collagen II expression, an increase of reactive oxygen species (ROS) production, inflammatory cytokine accumulation (IL-1ß, TNF-α), and apoptosis (Caspase3, Caspase8). However, tBHQ or Itaconate pretreated NP cells contained a higher level of Nrf2 protein and alleviated the negative effect caused by LPS, which was abolished with the silencing of Nrf2. Additionally, tBHQ showed a better ability to suppress ROS than Itaconate. Meanwhile, Itaconate inhibited a higher amount of IL-1ß and TNF-α than tBHQ. Interestingly, when NP cells were pretreated with both tBHQ and Itaconate, the result indicated an excellent anti-ROS and anti-inflammatory peculiarity. Furthermore, when NP cells suffered from LPS first and then treated with the agonist, the anti-ROS and anti-inflammatory effects remained. However, the cell viability, collagen II, and apoptotic degree were not improved. CONCLUSIONS: Both tBHQ and Itaconate effectively prevent NP cells from degeneration through anti-ROS and anti-inflammation, and the combined use of them may have better effects. But in comparison, their impact on reversing NP cell degeneration has yet to be proven.

Oral Tranexemic Acid With Triple Combination Cream (Flucinolone+Hydroquinone+Tretinoin) Versus Triple Combination Cream Alone In Treatment Of Melasma.

BACKGROUND: Melasma is an acquired cutaneous disorder characterized by hyperpigmentation of the face predominantly affecting the areas exposed to direct sun light. The triple combination cream, i.e., a mid-potency corticosteroid (Fluocinolone acetonide 0.01%), a retinoid (Tretinoin 0.05%), and Hydroquinone 4% is one of the widely used topical medicament for melasma treatment world over. Tranexamic acid is another agent found to be effective in melasma treatment when used topically, intra-lesionally or orally. This study has been conducted to compare mean decrease in Melasma Area Severity Index (MASI) score when tranexamic acid is combined with triple combination cream versus triple combination cream alone for melasma treatment. METHODS: A randomized controlled trial was conducted in a tertiary care hospital of Pakistan. Sixty-three patients of melasma who met the inclusion criteria and gave written informed consent for the study were enrolled. These patients were randomly divided into 2 treatment groups. Group A was given triple combination cream and oral tranxemic acid while Group B was given triple combination cream for duration of 8 weeks. Severity of melasma was assessed by MASI, which was calculated at baseline and at the end of week 8. Mean decrease in MASI score was calculated in both groups and statistically analysed employing SPSS 20. RESULTS: Sixty patients, 30 in both groups, completed the study. Study participants were predominantly female (81.67%), with mean age of 30.46±6.24 years in group A while 31.90±4.53 in group B. No statistically significant difference was noted in both treatment groups for mean decrease in the MASI score (6.4933±4.38358 in group A compared to 5.7833±5.04251 in the group B; p-value 0.56). CONCLUSIONS: The addition of oral tranexamic acid did not contribute significantly in decrease in MASI score when used in combination with topical triple regimen. It may have a role as an adjuvant to topical triple combination cream.

Antioxidant Combo Therapy Protects White Matter After Traumatic Brain Injury.

Following traumatic brain injury (TBI), increased production of reactive oxygen species (ROS) and the ensuing oxidative stress promotes the secondary brain damage that encompasses both grey matter and white matter. As this contributes to the long-term neurological deficits, decreasing oxidative stress during the acute period of TBI is beneficial. While NADPH oxidase (NOX2) is the major producer of ROS, transcription factor Nrf2 that induces antioxidant enzymes promotes efficient ROS disposal. We recently showed that treatment with an antioxidant drug combo of apocynin (NOX2 inhibitor) and TBHQ (Nrf2 activator) protects the grey matter in adult mice subjected to TBI. We currently show that this antioxidant combo therapy given at 2 h and 24 h after TBI also protects white matter in mouse brain. Thus, the better functional outcomes after TBI in the combo therapy treated mice might be due to a combination of sparing both grey matter and white matter. Hence, the antioxidant combo we tested is a potent therapeutic option for translation in future.

Hydroquinone: myths and reality.

Hydroquinone has pharmacological uses in disorders of pigmentation because of its ability to competitively inhibit the enzyme tyrosinase. Our contemporary review presents the strongest evidence supporting the use of hydroquinone with the most effective and tolerable formulations combining hydroquinone, retinoid and corticosteroid (modified Kligman formula or 'triple combination cream'). The risk of exogenous ochronosis is low if prescribed concentrations of ≤ 5 for a limited period with regular monitoring. Dermatologists should reassure patients that with controlled use, hydroquinone can be well-tolerated and safe for a range of hyperpigmentary conditions.

Randomized, Double-Blinded, Split-Face Study Comparing the Efficacy and Tolerability of Two Topical Products for Melasma.

BACKGROUND: Melasma is a common disorder of hyperpigmentation that disproportionately affects individuals with skin of color. There is a paucity of studies evaluating non-hydroquinone (HQ) topical therapies for the treatment of melasma in darker skin types. OBJECTIVE: To compare the safety, efficacy, and tolerability of a HQ-free, retinol-free cosmetic topical brightener (CTB) and HQ 4% in the treatment of moderate symmetric facial melasma in patients with Fitzpatrick skin types (FST) III–VI. Methods & Materials: This was a randomized, double-blinded, split-face clinical trial. Eighteen adult patients with facial melasma were treated with CTB and HQ 4%, each to a different side of the face, twice daily for 12 weeks. Clinical assessments included half-face Melasma Area Severity Index (MASI), Overall Hyperpigmentation scale, and Melasma Severity Rating Scale (MSRS). Patients completed a Melasma Quality of Life (MelasQoL) questionnaire and clinical photographs were taken at each visit. RESULTS: CTB and HQ 4% demonstrated statistically significant improvements in half-face MASI, Overall Hyperpigmentation, MSRS and MelasQol compared to baseline. HQ 4% showed statistically significant improvements in MSRS at week 12 compared to CTB, but was non-superior for all other clinical endpoints. CONCLUSION: HQ-free, retinol-free CTB and HQ 4% both are effective and well-tolerated in the treatment of moderate facial melasma in FST III–VI. J Drugs Dermatol. 2020;19(9):822-827. doi:10.36849/JDD.2020.5353.

Study of oral tranexamic acid, topical tranexamic acid, and modified Kligman's regimen in treatment of melasma.

BACKGROUND: Melasma is a pigmentary disorder affecting mainly face . Various treatment modalities available as topicals, superficial chemical peels and lasers but none till date gives promising results, until date quest for the best treatment modality is on. AIM: To study the effect of oral and topical Tranexamic acid (TXA) and modified Kligman's regimen in treatment of melasma. METHOD: Patients having melasma were enrolled after consent for voluntary participation. A detailed history and clinical examination was done. Total 60 patients were enrolled and randomized in three groups, 20 received oral TXA 250 mg twice daily, 20 topical TXA and 20 received modified Kligman's regimen for 8 weeks along with sunscreen MASI(Melasma area severity index) was calculated at baseline, at end of 4 & 8 weeks. MASI score was compared with that at the end of the study. Based on reduction in mean MASI the therapeutic response was graded. Pre and post treatment photographs was also compared. Statistical analysis done by using student square T test , ANOVA And TUKEY test. RESULTS: Reduction in MASI score was observed in all the groups but greater reduction in MASI score with modified Kligman's regimen by 30% followed with oral TXA by 25% reduction and least with topical TXA by 5%. CONCLUSION: Although modified Kligman's regimen is comparatively more efficient but due to its side effects in long term usage oral tranexamic acid could be a promising therapeutic approach for melasma.

Efficacy of 577 nm pro-yellow laser in the treatment of melasma: a prospective split-face study.

We aimed to study the effectiveness of 577 nm pro-yellow laser in the treatment of melasma. A total of 82 patients with melasma were included in this comparative study. A detailed medical history, examination, and calculation of Melasma Area and Severity Index were done for all patients. All participants were treated with topical sunscreen and hydroquinone 4% cream on both sides of the face. In addition, the left side of the face was subjected to a single pass of 577-nm pro-yellow laser at a monthly interval for three sessions. Follow up was done by comparing the Melasma area and severity index at 0, 3 and 6 months. At baseline, there is no significant difference in the Melasma area and severity index score between both sides of the face. At 3 months, MASI score was statistically significantly decreased on both sides of the face compared to pretreatment (P < .05). At 6 months, the mean MASI score at the laser-treated side was statistically significantly decreased compared to the non-laser-treated side (P < .05). we concluded that the addition of 577 nm pro-yellow laser in the treatment of melasma leads to maintain the improvement and reduction of the recurrence rate.

Microneedling with Drug Delivery (Hydroquinone 4% Serum) as an Adjuvant Therapy for Recalcitrant Melasma.

A 42-year-old woman with phototype V, presented a 9-year history of refractory centrofacial melasma to topical bleaching agents and peelings, untreated for the last 90 days. One session of microneedling with 1.5 mm needles was performed with hydroquinone 4% sterile serum drug delivery; after 3 days, modified Kligman's formula (hydroquinone 4% + fluocinolone acetonide 0.01% + tretinoin 0.05%) and broad-spectrum sunscreen SPF 70 were introduced for daily use. After 30 days, a significant improvement was observed in the clinical outcome (Figure 1) and the quality of life of the patient. These parameters were measured using Melasma Area and Severity Index (MASI) scale, with an 82.5% decrease, and Melasma Quality of Life Scale - Brazilian Population (MELASQoL-BP), with a 60% decrease. Dermatoscopic analysis (polarized videodermatoscopy x20) of the glabellar region revealed lighting of the pseudoreticular pigment network, diffuse light to dark brown background, and reduction in vascularity and telangiectasias (Figure 2). At the 5-month follow-up, there had been no relapse. The patient continued to use a broad-spectrum sunscreen along with the topical regiment.

Randomised, controlled, double-blind study of combination therapy of oral tranexamic acid and topical hydroquinone in the treatment of melasma.

BACKGROUND/OBJECTIVES: Melasma is a common pigmentary disorder for which oral tranexamic acid has shown some efficacy in previous studies. The aim of this study was to assess the effectiveness of oral tranexamic acid in combination with hydroquinone cream in the treatment of melasma. METHODS: Subjects with moderate-to-severe melasma were enrolled. Group A received hydroquinone 4% cream, sunscreen and oral tranexamic acid, while Group B received hydroquinone 4% cream, sunscreen and placebo capsules for 3 months. All subjects had an additional 3-month follow-up visit on sunscreen alone. The primary outcome measure was change in modified Melasma Area and Severity Index (mMASI) score. In addition, the melanin index was measured using a mexameter. RESULTS: Fifty subjects were enrolled, and all completed the study. There was a 55% reduction in mMASI after 3 months from mean 8.96 (SD 2.45) to 4.0 (SD 1.6) in Group A compared to 10.9% from mean 8.53 (SD 2.04) to 7.6 (SD 2.0) in Group B. Three months after oral and topical therapy was discontinued, there was a 42% decrease in mMASI compared to baseline in Group A (mean 5.1 SD 1.7) vs. 4.7% in Group B (mean 8.1 SD 2.0). No serious adverse events were observed. CONCLUSIONS: A combination of oral tranexamic acid and topical hydroquinone is more effective than hydroquinone alone in the treatment of melasma.

Melasma: A critical analysis of clinical trials investigating treatment modalities published in the past 10 years.

BACKGROUND: Melasma is an acquired disorder of facial pigmentation which is a treatment challenge. AIMS: The aim of this article is to critically appraise the clinical trial evidence for different treatment modalities for melasma, published in peer-reviewed journals in the past 10 years. PATIENTS/METHODS: The literature review was conducted using PubMed and MEDLINE. The search was performed in July 2019, and search parameters were limited to all English language articles published in the past 10 years only. RESULTS: Eighty-nine clinical trials were found. Four clinical trials investigated topical hydroquinone, supporting its safety and efficacy as first-line treatment. Twelve studies showed tranexamic acid as very promising. Nineteen studies assessed various novel oral, injectable, and topical treatments and highlight some new potential future treatments. Forty-two studies investigated laser and light treatment in melasma: LFQS laser is still one of the best options, especially in darker skin types. However, the picosecond laser has shown excellent results. Finally, 11 studies looked at peels. Overall, peels have not been shown to be superior to the use of topical therapy alone. CONCLUSION: Topical therapy with a HQ and retinoid-based product should be first line for a minimum of 3 months with the addition of oral tranexamic acid at 250 mg BD if no contraindication. Second-line treatment with lasers includes the LFQS Nd:YAG, picosecond laser, and the pulsed dye laser in lighter skin types. Third-line therapy would be the addition of chemical peels to the above treatments, with GA or TCA peels having the most evidence for effectiveness.

Topical metformin in the treatment of melasma: A preliminary clinical trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder characterized by symmetric hyperpigmented macules on the face. Triple combination cream (TCC) remains the gold standard treatment but its prolonged use often causes adverse effects. Recently, studies have shown that topical metformin has melanopenic action. AIMS: To evaluate the safety and efficacy of topical metformin in the treatment of melasma and to compare its efficacy with TCC (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%). METHODS: This was a randomized controlled study conducted on 40 patients with melasma aged more than 18 years. Patients in group 1 (n = 20) were treated with 30% metformin lotion, whereas group 2 patients (n = 20) were treated with TCC for 8 weeks. Pigmentation was assessed using Melasma Area and Severity Index (MASI) at baseline and after 8 weeks. Outcome measures included global improvement scale (grades 1-4) and patient satisfaction. Safety was assessed according to adverse events and patch testing. RESULTS: All 40 patients completed the study. Out of 20 patients in group 1, 11 showed grade 1 improvement (1% to <25%) and grade 2 (25%-50%) and grade 3 (>50%-75%) improvements were seen in one patient each. In group 2, grades 1, 2, 3, and 4 improvements were seen in 14, 2, 1, and 1 patients, respectively. However, the difference was not statistically significant. Adverse events were noted in three patients in group 2 and none in group 1. CONCLUSION: Topical metformin is a novel, safe, and almost as effective modality as TCC to treat melasma.

Prospective randomized controlled trial comparing treatment efficacy and tolerance of picosecond alexandrite laser with a diffractive lens array and triple combination cream in female asian patients with melasma.

BACKGROUND: Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC: fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions. OBJECTIVE: We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma. METHODS: Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals) or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12 and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively. RESULTS: Nine, 11 and 6 participants in groups A1, A2 and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2 and B, the improvement rates at week 20 were 53%, 38% and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores and brown spots after 3 laser sessions (P < 0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles and pores; however, only red areas were significantly different (P < 0.001). All side-effects in the 3 groups were transient and gradually subsided after 1-3 months. CONCLUSION: Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions.

The efficacy and safety of topical 5% methimazole vs 4% hydroquinone in the treatment of melasma: A randomized controlled trial.

BACKGROUND: The management of melasma is still challenging, and new treatment modalities with favorable side effect profile are required. Methimazole, a peroxidase inhibitor, seems to have a beneficial effect in the management of melasma but there is a paucity of studies for evaluation of its efficacy. This double-blinded trial was aimed to evaluate the efficacy and safety of methimazole vs hydroquinone 4% which is the gold standard treatment in the management of melasma. METHODS: Fifty patients with melasma were enrolled and randomly divided into two groups to receive 4% hydroquinone or 5% methimazole once daily for 8 weeks. Forty patients completed the study. The clinical response was assessed at 4th, 8th, and 12th weeks after treatment by MASI score, patient satisfaction, and physician scores. RESULTS: Both groups showed a reduction in the MASI score at the 8th week which was more significant in hydroquinone group but higher relapse rate was also observed in this group after discontinuing the drug. The side effects were similar between groups. Also, patient and physician satisfaction scores were also more in favor of hydroquinone 4%. CONCLUSION: Methimazole could be an alternative treatment of melasma alone or in combination with other depigmenting drugs. Although not as effective as hydroquinone, the noncytotoxic and nonmutagenic aspects of methimazole may make it a promising alternative for the treatment of melasma.

Efficacy and tolerability on melasma of a topical cosmetic product acting on melanocytes, fibroblasts and endothelial cells: a randomized comparative trial against 4% hydroquinone.

BACKGROUND: Recent data demonstrated that an altered basal membrane, activated melanocytes and secreted factors from keratinocytes but also fibroblasts and endothelial cells are involved in the pathophysiology of melasma. OBJECTIVES: To evaluate the efficacy and tolerability on melasma of a new topical skin-lightening cosmetic product combination (CCP) targeting several factors identified to be involved in melasma pathogenesis compared to 4% hydroquinone (HQ). METHODS: Forty-three women with melasma were enrolled in a 12-week double-blind, randomized, parallel-group trial and treated with CCP or 4% HQ cream. Efficacy was evaluated with the modified Melasma Area Severity Index (mMASI) score and colorimetric change. Cutaneous tolerability and patient satisfaction were also investigated. RESULTS: The mMASI score decreased for both products from baseline and over the study period. At week 12, 90% of the subjects who received the combination products had an improvement in pigmentation vs. 79% with HQ. Similarly, both products significantly increased Individual Typological Angle parameters. For both measures, no statistically significant difference was observed between CCP and HQ in terms of change from baseline. CPP was very well tolerated. CONCLUSIONS: Cosmetic product combination is as effective as HQ in the management of facial dyspigmentation and represents a safe alternative.

Randomized control trial outcomes of tranexamic acid combination serum as a depigmenting agent for the use in healthy individuals.

To compare the effectiveness of tranexamic acid (TA) combination serum with hydroquinone, the gold standard in whitening agents for healthy populations. This was a three-arm randomized controlled trial. The subjects were divided into three groups: the first group received 3% TA combination serum (3% TA, 4% galactomyces ferment filtrate, 2% niacinamide, and 4% alpha arbutin), the second group received 2% TA combination serum, and the third group received 4% hydroquinone. One milliliter of each serum was applied on three holes: Hole A, which was located 4 cm from the left cubital fossa, Hole B, which was located 4 cm from the first hole, and Hole C, which was located 4 cm from the right cubital fossa. The skin brightness and pigmentation intensity were evaluated each week for 4 weeks using a chromameter. A total of 44 subjects were recruited for this study. All groups showed a significant improvement in skin brightness and pigmentation intensity after 4 weeks (p < .001). There were no differences between the treatment groups and hydroquinone (p > .05). TA serum (2 and 3%) combined with 4% galactomyces ferment filtrate, niacinamide, and alpha arbutin is an effective depigmenting agent.

Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress, inflammation, and apoptosis.

Diabetic patients are more susceptible to renal ischemia/reperfusion (I/R) injury (RI/RI) and have a poor prognosis, but the underlying mechanism remains unclear. The present study aimed to examine whether diabetes could worsen acute kidney injury induced by I/R in rats and clarify its mechanism. Control and streptozotocin-induced diabetic rats were subjected to 45 min renal pedicle occlusion followed by 24 h reperfusion. Tert-butylhydroquinone (TBHQ, 16.7 mg/kg) was administrated intraperitoneally 3 times at intervals of 8 h before ischemia. Serum and kidneys were harvested after reperfusion to evaluate renal function and histological injury. Enzyme-linked immunosorbent assays were used to test pro-inflammatory cytokines. Terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assays were used to detect apoptotic cells, and western blotting was performed to determine the expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3, as well as oxidative stress and inflammation-related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB). Compared with control animals, diabetic rats undergoing I/R exhibited more severe tubular damage and renal dysfunction. Diabetes exacerbated oxidative stress, the inflammatory response, and apoptosis after renal I/R by enhancing TLR4/NF-κB signaling and blocking the Nrf2/HO-1 pathway. RI/RI in diabetic rats was attenuated by pretreatment with TBHQ (a Nrf2 agonist), which exerted anti-inflammatory and anti-apoptotic properties by inhibiting NF-κB signaling. These findings indicate that hyperglycemia exacerbates RI/RI by intensifying oxidative stress, inflammation, and apoptosis. Antioxidant pretreatment may alleviate RI/RI in diabetic patients.