. 2021 Jun 25;22(13):6839.

doi: 10.3390/ijms22136839.

RETRACTED: Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart

Ali H El-Far¹, Yaser H A Elewa^{2

3}, Elsayeda-Zeinab A Abdelfattah⁴, Abdel-Wahab A Alsenosy¹, Mustafa S Atta⁵, Khalid M Abou-Zeid⁴, Soad K Al Jaouni⁶, Shaker A Mousa⁷, Ahmed E Noreldin⁸

Affiliations

¹ Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.
² Department of Histology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
³ Laboratory of Anatomy, Faculty of Veterinary Medicine, Basic Veterinary Sciences, Hokkaido University, Sapporo 060-0818, Japan.
⁴ Animal Care Unit, Medical Research Institute, Alexandria University, Alexandria 21544, Egypt.
⁵ Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
⁶ Department of Hematology/Pediatric Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁷ Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
⁸ Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.

PMID: 34202112
PMCID: PMC8268720
DOI: 10.3390/ijms22136839

RETRACTED: Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart

Ali H El-Far et al. Int J Mol Sci. 2021.

. 2021 Jun 25;22(13):6839.

doi: 10.3390/ijms22136839.

Authors

Affiliations

¹ Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.
² Department of Histology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
³ Laboratory of Anatomy, Faculty of Veterinary Medicine, Basic Veterinary Sciences, Hokkaido University, Sapporo 060-0818, Japan.
⁴ Animal Care Unit, Medical Research Institute, Alexandria University, Alexandria 21544, Egypt.
⁵ Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
⁶ Department of Hematology/Pediatric Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁷ Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
⁸ Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.

PMID: 34202112
PMCID: PMC8268720
DOI: 10.3390/ijms22136839

Retraction in

RETRACTED: El-Far et al. Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart. Int. J. Mol. Sci. 2021, 22, 6839.
El-Far AH, Elewa YHA, Abdelfattah EA, Alsenosy AA, Atta MS, Abou-Zeid KM, Jaouni SKA, Mousa SA, Noreldin AE. El-Far AH, et al. Int J Mol Sci. 2024 Dec 5;25(23):13063. doi: 10.3390/ijms252313063. Int J Mol Sci. 2024. PMID: 39660544 Free PMC article.

Abstract

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.

Keywords: D-galactose; anti-aging; curcumin; oxidative stress; thymoquinone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Chemical Structure. (A) thymoquinone (PubChem CID; 10281). (B) curcumin (PubChem CID; 969516).

**Figure 2**
Serum biochemical parameters. (A) glucose (mg/dL). (B) ALT (U/L). (C) AST (U/L). (D) urea (mg/dL). (E) creatinine (mg/dL). (F) uric acid (mg/dL). Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. control. ⁺ p < 0.05, ⁺⁺ p < 0.01, and ⁺⁺⁺ p < 0.001 vs. vehicle. ^x p < 0.05 and ^xx p < 0.01 vs. D-gal. ^ɸɸɸ p < 0.001 vs. D-gal+TQ. ^## p < 0.01 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 5.

**Figure 3**
Immunohistochemical staining of rat cerebellum by caspase 3. (A) negative control group. (B) vehicle group. (C) D-gal group revealing strong caspase 3 reaction in Purkinje cells layer (PCL), in granular cells layer (GL) and in molecular cells layer (ML). (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of caspase 3 in the cerebellum in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺ p < 0.01 and ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^ɸɸɸ p < 0.001 vs. D-gal+TQ. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 4**
Immunohistochemical staining of rat cerebellum by calbindin. (A) negative control group showing high reaction in calbindin in many Purkinje cells (arrow). (B) vehicle group. (C) D-gal group revealing no calbindin reaction in necrotic Purkinje cells (arrowhead). (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of positive Purkinje cells in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^ɸ p < 0.05 vs. D-gal+TQ. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 5**
Immunohistochemical staining of rat cerebellum by ionized calcium-binding adapter molecule 1 (IBA1). (A) negative control group showed few microglia. (B) vehicle group. (C) D-Gal group showed many positive microglia. (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of IBA1 in the cerebellum in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. ** p < 0.01 and *** p < 0.001 vs. control. ⁺ p < 0.05 and ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^ɸɸɸ p < 0.001 vs. D-gal+TQ. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 6**
Immunohistochemical staining of rat hippocampus by caspase 3. (A) negative control group. (B) vehicle group. (C) D-gal group revealing strong caspase 3 reaction. (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of caspase 3 in the hippocampus in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^ɸɸɸ p < 0.001 vs. D-gal+TQ. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 7**
Immunohistochemical staining of rat hippocampus by calbindin. (A) negative control group showing the high reaction of calbindin. (B) vehicle group. (C) D-gal group showed many positive microglia. (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of positive cells in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 8**
Immunohistochemical staining of rat hippocampus by ionized calcium-binding adapter molecule 1 (IBA1). (A) the negative control group showed few microglia. (B) vehicle group. (C) D-gal group showed many positive microglia. (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of IBA1 in the hippocampus in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^ɸɸɸ p < 0.001 vs. D-gal+TQ. ***^###*** p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 9**
Immunohistochemical staining of rat heart by Bcl2. (A) negative control group. (B) vehicle group. (C) D-gal group. (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of Bcl2 in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^ɸɸɸ p < 0.001 vs. D-gal+TQ. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 10**
Immunohistochemical staining of rat heart by caspase 3. (A) negative control group. (B) vehicle group. (C) D-gal group revealing strong caspase 3 reaction in nuclei. (D) D-gal+TQ group. (E) D-gal+Cur group. (F) D-gal+TQ+Cur group. (G) Quantification of caspase 3 in the heart in different groups. Scale bar = 50 µm. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. *** p < 0.001 vs. control. ⁺⁺⁺ p < 0.001 vs. vehicle. ^xx p < 0.01 and ^xxx p < 0.001 vs. D-gal. ^### p < 0.001 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 10.

**Figure 11**
Expression of fold changes of brain (A) *TP53*, (B) *p21*, (C) *BCL2*, (D) *Bax*, and (E) *CASP-3*. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. control. ⁺ p < 0.05, ⁺⁺ p < 0.01, and ⁺⁺⁺ p < 0.001 vs. vehicle. ^xxx p < 0.001 vs. D-gal. ^# p < 0.05 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 5.

**Figure 12**
Expression of fold changes of heart (A) *TP53*, (B) *p21*, (C) *BCL2*, (D) *Bax*, and (E) *CASP-3*. Data were analyzed with one-way ANOVA, followed by Tukey’s multiple comparison test. * p < 0.05 and *** p < 0.001 vs. control. ⁺⁺ p < 0.01 and ⁺⁺⁺ p < 0.001 vs. vehicle. ^x p < 0.05, ^xx p < 0.01, and ^xxx p < 0.001 vs. D-gal. ^## p < 0.01 vs. D-gal+TQ+Cur. Error bars represent mean ± SD. n = 5.

**Figure 13**
Experimental design scheme. D-gal; D-galactose, S/C; subcutaneous, TQ; thymoquinone, Cur; curcumin, B.W.; body weight.

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Retracted article

RETRACTED: Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart

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RETRACTED: Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats' Brain and Heart

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